Hemodialysis system

ABSTRACT

A drain cassette for a dialysis unit has a fluid channel between venous and arterial connection ports, and a valve may controllably open and close fluid communication between a drain outlet port and the venous connection port or the arterial connection port. A blood circuit assembly and drain cassette may be removable from the dialysis unit, e.g., by hand and without the use of tools. A blood circuit assembly may include a single, unitary member that defines portions of a pair of blood pumps, control valves, channels to accurately position flexible tubing for an occluder, an air trap support, and/or other portions of the assembly. A blood circuit assembly engagement device may assist with retaining a blood circuit assembly on the dialysis unit, and/or with removal of the assembly. An actuator may operate a retainer element and an ejector element that interact with the assembly.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/122,166, filed Nov. 25, 2013 and entitled “Hemodialysis System,” nowU.S. Pat. No. 9,724,458 issued Aug. 8, 2017, which is a National Stageof International Patent Application No. PCT/US2012/039369, filed May 24,2012 and entitled “HEMODIALYSIS SYSTEM” which claims priority under 35U.S.C. §119(e) to U.S. Provisional Patent Application No. 61/489,464,filed May 24, 2011 and entitled “HEMODIALYSIS SYSTEM.” Each of theseapplications is incorporated herein by reference in its entirety for allpurposes.

FIELD OF INVENTION

The present invention generally relates to hemodialysis and similardialysis systems, e.g., systems able to treat blood or other bodilyfluids extracorporeally.

BACKGROUND

Many factors make hemodialysis inefficient, difficult, and expensive.These factors include the complexity of hemodialysis, the safetyconcerns related to hemodialysis, and the very large amount of dialysateneeded for hemodialysis. Moreover, hemodialysis is typically performedin a dialysis center requiring skilled technicians. Therefore anyincrease in the ease and efficiency of the dialysis process could havean impact on treatment cost or patient outcome.

SUMMARY OF INVENTION

Aspects of the invention generally relate to hemodialysis and similardialysis systems. Illustrative embodiments described herein involve, insome cases, interrelated products, alternative solutions to a particularproblem, and/or a plurality of different uses of one or more systemsand/or articles. Although the various systems and methods describedherein are described in relation to hemodialysis, it should beunderstood that the various systems and method described herein areapplicable to other dialysis systems and/or in any extracorporeal systemable to treat blood or other bodily fluids, such as hemofiltration,hemodiafiltration, etc.

In one aspect of the invention, a drain cassette for a dialysis unitincludes a venous connection port for connection to, and fluidcommunication with, a venous blood line connector, an arterialconnection port for connection to, and fluid communication with, anarterial blood line connector, a fluid channel fluidly connecting thevenous connection port and the arterial connection port, a drain outletport in fluid communication with the fluid channel and arranged toremovably couple with a drain connector on an exposed panel of thedialysis unit, and a valve arranged to control flow in the fluidchannel. The valve may be arranged to control in the fluid channel toeither controllably open and close fluid communication in the fluidchannel between the drain outlet port and the venous connection port, orto controllably open and close fluid communication in the fluid channelbetween the drain outlet port and the arterial connection port. Such anarrangement may allow for purging and/or rinsing of venous and arteriallines to drain, e.g., in preparation for a treatment. In addition, thedrain cassette may be removable from the dialysis unit, allowing anoperator to remove and replace blood-contacting portions of the draincassette when preparing the dialysis unit for treating another patient.

In one embodiment, the drain cassette may include a body that definesthe arterial and venous connection ports and the fluid channel. A checkvalve may be arranged to allow flow from the fluid channel and out ofthe drain outlet port and to resist flow from the drain outlet port tothe fluid channel. Thus, fluid or other material in a drain linedownstream of the check valve may be prevented from entering the fluidchannel. The valve that controls flow in the fluid channel may be apneumatically-controlled valve, and a pneumatic control port on thedrain cassette may be arranged to removably mate with a port on theexposed panel of the dialysis unit and fluidly couple the valve with theport on the exposed panel to allow control of the valve.

In one embodiment, the drain cassette may include a latch arranged toreleasably lock the drain cassette to the exposed panel. For example,the latch may include a handle and a male bayonet-type connectorarranged to engage with a female bayonet-type receiver on the panel ofthe dialysis unit. Thus, the latch may be operated, e.g., by insertingthe bayonet connector into the receiver and turning the handle, to bothconnect and disconnect the drain cassette with respect to the panel.Such mounting and dismounting of the cassette may also causecoupling/uncoupling of one or more ports, electrical connectors or othercomponents of the drain cassette with a corresponding port, connector,etc. on the panel. For example, a drain port, pneumatic valve controlport and electrical connector coupled with one or more sensors in thedrain cassette may simultaneously couple with correspondingports/connectors on the panel in a single connection operation, whichmay include pushing the drain cassette onto the panel and turning thelatch handle.

The drain outlet port may fluidly communicate with the fluid channel ata point above where the arterial and venous connection ports communicatewith the fluid channel, e.g., so that air in the fluid channel may beevacuated by introducing fluid at the connection ports. In oneembodiment, the fluid channel has a U shape with the arterial and venousconnection ports fluidly connected to the fluid channel at ends of the Ushape, and the drain outlet port fluidly connected to the fluid channelat a central bend of the U shape.

One or more sensors may be included to detect characteristics of fluidin the fluid channel or elsewhere in the drain cassette. For example, aconductivity sensor may be arranged to detect a conductivity of fluid inthe fluid channel, and a temperature sensor may be arranged to detect atemperature of fluid in the fluid channel. The one or more sensors maybe coupled to an electrical connector arranged to electrically connectthe one or more sensors to a corresponding electrical connector on theexposed panel. In one embodiment, the electrical connector and the drainoutlet port are arranged to simultaneously couple with a correspondingelectrical connector and drain connector on the exposed panel of thedialysis unit in a single connection operation. In some arrangements, apneumatic control port coupled to the valve may be arranged to removablymate with a control port on the exposed panel, and to simultaneouslycouple with the corresponding control port in the same single connectionoperation used to connect the drain port and electrical connector.

The valve may be arranged so that the drain outlet port is inpermanently open fluid communication with the arterial connection port,and the valve may controllably open and close fluid communication in thefluid channel between the drain outlet port and the venous connectionport. Alternately, the drain outlet port may be in permanently openfluid communication with the venous connection port, and the valve maybe arranged to controllably open and close fluid communication in thefluid channel between the drain outlet port and the arterial connectionport.

In another aspect of the invention, a blood circuit assembly and a draincassette may be engageable with an exposed panel of a dialysis unit foroperation in a dialysis treatment, and may be removable from the exposedpanel for replacement without the use of tools. Such an arrangement mayallow for easy replacement of all blood-contacting components of adialysis unit so that the dialysis unit can be used for multiple,different patients (e.g., in a clinical setting) while minimizing riskof a prior patient's blood borne materials from coming into contact witha subsequent patient's treatment components. For example, the bloodcircuit assembly may include a pair of pneumatic pumps for circulatingblood received from a patient through a circuit including a dialyzerunit and returned to the patient, an air trap arranged to remove airfrom blood circulating in the circuit, a pair of dialyzer connectionsarranged to connect to the inlet and outlet of a dialyzer unit, and apair of blood line connectors, including an arterial blood lineconnector for receiving blood from the patient and providing blood tothe pneumatic pumps and a venous blood line connector for returningblood to the patient. The pneumatic pumps may have pneumatic controlports arranged for alignment and mating with corresponding ports locatedon an exposed panel of the dialysis unit by pushing the control portsinto engagement with the corresponding ports with mounting of the bloodcircuit assembly to the exposed panel. Thus, the blood circuit assemblymay be relatively easily mounted to, and dismounted from, the panel ofthe dialysis unit. The drain cassette may include a venous connectionport for connection to, and fluid communication with, the venous bloodline connector, an arterial connection port for connection to, and fluidcommunication with, the arterial blood line connector, a fluid channelfluidly connecting the venous connection port and the arterialconnection port, a drain outlet port in fluid communication with thefluid channel and arranged to removably couple with a drain connector onan exposed panel of the dialysis unit, and a valve arranged to controlflow in the fluid channel Like the blood circuit assembly, and discussedabove, the drain cassette may be arranged to be easily mounted to thepanel of the dialysis unit for control by the dialysis unit in thetreatment process, and dismounted from the panel for replacement.

In one embodiment, flexible tubing may fluidly connect the pumps, theair trap, the dialyzer connections and the blood line connectors of theblood circuit assembly. For example, the flexible tubing may fluidlyconnect the arterial blood line connector to an inlet for the pumpcassette, an outlet for the pump cassette to a dialyzer inlet connector,a dialyzer outlet connector to an inlet of the air trap, and an outletof the air trap to the venous blood line connector. The blood lineconnectors may be arranged for a threaded luer-type connection to apatient access, and arranged for a press-in type connection to the draincassette connection ports. Such arrangement may allow for easyconnection to the drain cassette, as well as allow for disinfection ofthe connectors, e.g., the press-in connection to the drain cassette mayallow disinfecting fluid to flow around the patient access connectionpart of the connector. The drain cassette may include other featuresmentioned above.

In another aspect of the invention, a blood circuit assembly for adialysis unit includes a pair of pneumatic pumps for circulating bloodreceived from a patient through a circuit including a dialyzer unit andreturning the blood to the patient, an air trap arranged to remove airfrom blood circulating in the circuit, a pair of dialyzer connectionsarranged to connect to the inlet and outlet of a dialyzer unit, a pairof blood line connectors, including an arterial blood line connector forreceiving blood from the patient and providing blood to the pneumaticpumps and a venous blood line connector for returning blood to thepatient, and flexible tubing fluidly connecting the pumps, the air trap,the dialyzer connections and the blood line connectors. The pneumaticpumps may have pneumatic control ports arranged for alignment and matingwith corresponding ports located on an exposed panel of the dialysisunit by pushing the control ports into engagement with the correspondingports with mounting of the blood circuit assembly to the exposed panel.

Also, the pumps may be defined, at least in part, by a single unitarymember that additionally defines a plurality of routing channels for atleast a portion of the flexible tubing. In one embodiment, the singleunitary member or other organizing tray configuration defines an airtrap cavity that receives the air trap. In some arrangements, the inletof the air trap is supported by the air trap cavity or other support ata position above an outlet of the air trap when the blood circuitassembly is mounted to a dialysis unit. This configuration may makeremoval of air from the blood lines more effective.

In another embodiment, the single unitary member may define thepneumatic control ports for the pumps, a concave chamber portion for thepumps, a chamber portion of a plurality of valves used to control flowthrough the pumps, routing channels for flexible tubing to position thetubing for engagement with an occluder when the assembly is mounted tothe dialysis unit, and/or other features. For example, the organizingtray may include circuit tube engagement members having a hole throughwhich a respective circuit tube passes that engage with the tube toallow the circuit tube to be pulled and stretched for engagement with anoccluder of the dialysis unit. Having a single part define multipleportions of the blood circuit assembly and/or to accurately routeflexible tubing may make assembly of the blood circuit assembly easierand more effective, e.g., by ensuring that various components areproperly positioned on the panel of the dialysis unit.

In another embodiment, the flexible tubing may connect components asfollows: the arterial blood line connector may be connected to an inletfor the pump cassette, an outlet for the pump cassette may be connectedto a dialyzer inlet connector, a dialyzer outlet connector may beconnected to an inlet of the air trap, and an outlet of the air trap maybe connected to the venous blood line connector.

In some embodiments, the blood circuit assembly may include ananticoagulant connection for engaging with an anticoagulant source andproviding anticoagulant into the circuit. For example, a pump forpumping anticoagulant from the anticoagulant source to the circuit maybe included, e.g., as part of a pump cassette. The anticoagulantconnection may include a vial holder and a spike, and the anticoagulantsource may be a vial of heparin.

In another aspect of the invention, a blood circuit assembly engagementdevice for a dialysis unit includes an actuator, movable between aretention position and an ejection position, mounted to a panel of thedialysis unit adjacent a plurality of control ports, a retainer elementcoupled to the actuator and arranged, with the actuator in the retentionposition, to retain a blood circuit assembly mounted to the panel of thedialysis unit on the panel, and arranged, with the actuator in theejection position, to release the blood circuit assembly for removalfrom the panel of the dialysis unit, and an ejector element coupled tothe actuator and arranged, with the actuator moved from the retentionposition to the ejection position, to urge the blood circuit assemblyaway from the panel. Such an arrangement may make mounting, retentionand removal of a blood circuit assembly with respect to a dialysis unitmore accurate and effective. For example, if the retainer element is notpositioned in the retention position with a blood circuit assemblymounted to the panel, a user can easily verify that the assembly is notproperly engaged with the panel. The actuator can then be used to ejectthe assembly, allowing replacement of the assembly on the panel.

In one embodiment, the actuator is pivotally mounted to the panel, andthe retainer element is fixed to the actuator. The ejector element maybe pivotable between an inactive position and an ejection position, andpivoted based on movement of the actuator. For example, the actuator maybe arranged to be moved from the retention position and the ejectionposition by a user's thumb. In one arrangement, first and second bloodcircuit assembly engagement devices are provided on the panel, with thefirst engagement device arranged on a first side of a blood circuitassembly mounted to the panel, and the second engagement device arrangedon a second side of the blood circuit assembly. The first and secondsides may be opposed to each other such that the actuators of theengagement devices are movable by respective first and second thumbs ofa user. For example, using both thumbs, a user may press on theactuators to move the actuators away from each other to move theactuators from respective retention positions to ejection positions. Theejection members may be arranged to contact a portion of a pump chamberin the ejection position, e.g., a rear chamber wall portion of the pump,and the retention elements may be arranged, with the actuator in theretention position and a blood circuit assembly mounted to the panel, tocontact an outer surface of the blood circuit assembly to lock the bloodcircuit assembly in place.

Also described herein are occlusion assemblies configured to facilitatethe opening and closing by occlusion of flexible tubing. In particularembodiments, the occlusion assemblies are associated with or form partof a medical infusion device, such as a hemodialysis device, peritonealdialysis device, plasmapheresis device, etc., and may be controllablyand automatically operated to facilitate fluid handling by such devices.The occlusion assemblies may be designed to position and immobilized thetubing and may include a frame or other support feature providing tubingguides and/or configured for attachment to or integration with a fluidhandling assembly of a device of which they are part or with which theyare used. The occlusion assemblies comprise a tubing occluder, which maybe a mechanism constructed and positioned to apply a force to thetube(s) associated with the occlusion assembly to occlude the tubes andto release the force to allow the tubes to open for fluid flow. Theocclusion assemblies and tubing occluders may be configured to include asingle tube in certain cases, and in other cases to occlude multipletubes, whether an odd number of tubes or an even number of tubes.Certain occlusion assemblies are specifically configured for occludingone or more pairs of tubes and may include tubing occluders having aseparate occluding member for occluding each of the pair of collapsibletubes. The occlusion assemblies may include automatic actuators foroperating the tubing occluders, and in certain cases also include amanual actuator to provide an override function. The occlusionassemblies may include a door designed and positioned to cover at leasta portion of the tubes be included and tubing occluder mechanism. Suchocclusion assemblies may include safety features, for example, toprevent a release of occlusion force on the tubing when the door is notin a closed position and/or convenience features, for example a retainermechanism to hold the tube occluder in a non-occluding position when thedoor is open with the tube occluder in the non-occluding position.

In one aspect, a variety of occlusion assemblies for occluding at leastone collapsible tube of a medical infusion device are described. Incertain embodiments, the occlusion assembly is configured for occludingat least one pair of collapsible tubes and comprises, for each pair ofcollapsible tubes, a first occluding member and a second occludingmember, the first occluding member positioned adjacent to a firstcollapsible tube of the pair and the second occluding member positionedadjacent to a second collapsible to the pair, when the tubes areinstalled in the occlusion assembly for operation. The first occludingmember and the second occluding member are further positioned adjacentfrom each other such that a space is defined between them. These spaceis on an opposite side of each occluding member then is the collapsibletubes to which it is adjacent. The occlusion assembly further comprisesa spreader positioned within the space between the occluding members andmovable from a first position to a second position, wherein movementfrom the first position to the second position causes the spreader toforce at least a portion of the first and second occluding members tomove apart from each other to increase the size of the space betweenthem and forced a tube-contacting portion of each occluding memberagainst the collapsible tube to which it is adjacent to occlude thecollapsible tube. The occlusion assembly further comprises at least oneactuator constructed and positioned to move the spreader between thefirst and second positions.

In certain embodiments the occlusion assembly is configured foroccluding at least one collapsible tube and comprises a frame comprisinga tubing guide configured for positioning the collapsible tube, a tubingoccluder mounted to the frame and comprising an occluding memberconstructed and positioned to controllably occlude or release occlusionof the collapsible tube, a door hingeably mounted to the frame andpositioned to cover at least a portion of the collapsible tube andtubing occluder when in a closed position and to provide user access tothe collapsible tube when in an open position, and a switch configuredand positioned to detect when the door is in a closed position and topermit operation of the tubing occluder to release occlusion of thecollapsible tube only when the door is in the closed position.

In certain embodiments and occlusion assembly for collapsing at leastone collapsible tube comprises a tubing occluder comprising an occludingmember constructed and positioned to controllably occlude or releaseocclusion of the collapsible tube, and automatic actuator operativelycoupled to the tubing occluder to cause essentially linear motion of atleast a portion of the tubing occluder to cause the occluding member tomove from an occluding position to a non-occluding position, and anoverride mechanism operatively coupled to the tubing occluder to causeessentially linear motion of at least a portion of the tubing occluderto cause the occluding member to move from an occluding position to anon-occluding position upon manual operation of the override mechanismby a user.

In certain embodiments, and occlusion assembly for occluding at leastone collapsible tube comprises a frame comprising a tubing guideconfigured for positioning the collapsible tube, a tubing occludermounted to the frame and comprising an occluding member constructed andpositioned to controllably occlude or release occlusion of thecollapsible tube, a door hingeably mounted to the frame and positionedto cover at least a portion of the collapsible tube and tubing occluderwhen in a closed position and to provide user access to the collapsibletube when in an open position, and a retainer mechanism engaged by thedoor when the door is in the closed position and configured to permitoperation of the tubing occluder to occlude or release occlusion of thecollapsible tube when the door is in the closed position and configuredto engage and retain the tubing occluder in a non-occludingconfiguration when the door is opened while the tubing occluder ispositioned in the non-occluding configuration.

In another aspect a method of operating an occlusion assembly foroccluding at least one pair of collapsible tubes of a medical infusiondevices disclosed. In one embodiment, the method involves moving aspreader of the occlusion assembly from a first position to a secondposition, wherein the spreader is positioned within a space definedbetween a first occluding member and a second occluding member to causethe spreader to force at least a portion of the first and secondoccluding members to move apart from each other to increase the size ofthe space between them and force a tube-contacting portion of eachoccluding member against a collapsible tube to which it is adjacent toocclude the collapsible tube.

In another aspect of the invention, an enclosure for containing aportable hemodialysis unit is provided, where the hemodialysis unitincludes suitable components for performing hemodialysis including adialyzer, one or more pumps to circulate blood through the dialyzer, asource of dialysate, and one or more pumps to circulate the dialysatethrough the dialyzer. The enclosure may include a housing that supportsthe components of the hemodialysis unit and has a front panel at whichblood circuit connections and dialysate fluidic connections are located.For example, the front panel may support blood line connections forpatient blood access, connections for a reagent supply, dialyzerconnections for both blood flow and dialysate, etc. Thus, in oneembodiment, an operator may complete all necessary fluid circuitconnections for the blood circuit and reagent supply at the housingfront panel. The enclosure may also include a pair of vertical,side-by-side doors hingedly mounted to the housing at opposite sides ofthe front panel so that the doors are movable between open and closedpositions. With the doors in an open position, an operator may haveaccess to the blood circuit connections and dialysate fluidicconnections. Also, with the doors in the closed position, access to thepatient access and dialysate fluidic connections may be blocked, and thedoors may allow for the retention of heat in the housing suitable fordisinfection during a disinfection cycle. For example, at least one ofthe doors may include a seal to resist air exchange between an interiorand an exterior of housing when the doors are in the closed position tohelp retain heat and/or help resist entry of dust, dirt or othercontaminants.

In one embodiment, each of the vertical, side-by-side doors is mountedto the housing via a hinge plate that is pivotally mounted to the doorat a first end, and is pivotally mounted to the housing at a second endopposite the first end. Thus, the doors may be positionable at two openpositions, e.g., a first open position in which blood circuitconnections and dialysate fluidic connections are exposed and the hingeplate is adjacent the housing, and a second open position in which thehinge plate is positioned away from the housing. One or more retainermembers may be included to maintain the doors in an open positionrelative to a corresponding hinge plate. For example, the retainermember may include at least one magnet attached to the door or the hingeplate that tends to keep the door in an open position relative to thehinge plate and the housing. Also, one or more retainer members maymaintain the hinge plates in a closed position relative to the housing,e.g., in a position close to the housing, and/or maintain the hingeplates in an open position away from the housing.

In one embodiment, at least one of the doors may include a containerholder that is movable between a folded position and an extendedposition in which the container holder is arranged to support acontainer, such as reagent supply container. In addition, oralternately, one or both of the doors may include a hook to support acontrol interface for the hemodialysis unit, such as a remote interfaceunit that is connected to the housing by a communication cable. Thesefeatures may make use of the dialysis unit easier by supportingcomponents in a convenient location.

In another embodiment, the front panel may include at least one flangedportion to support blood lines of a blood circuit assembly. For example,the front panel may include several flanged sections arranged at aperiphery of the front panel, such as at lower corners and at a top edgeof the front panel. Blood circuit lines that connect to a patient may berelatively long (e.g., up to 3-4 feet or more), and may be wrappedaround the periphery of the front panel and retained in place by theflanged portions. The flanged portions may be arranged to support theblood lines and allow the doors to be moved to the closed positionwithout contacting the blood lines, e.g., to avoid pinching of the bloodlines at door hinge points.

In one embodiment, the blood circuit connections at the front panelinclude arterial and venous blood line connectors for the blood circuit,and the dialysate fluidic connections at the front panel include aconnection point for a reagent supply, dialyzer dialysate connections,and a blood line connection point for connecting the arterial and venousblood lines to a directing circuit of the dialysis unit.

The hemodialysis unit may include a control interface that is connectedto the housing by a flexible cable and that is arranged to allow a userto receive information from and provide information to the hemodialysisunit. In one embodiment, the enclosure may include a control interfacemounting area at a top of the enclosure where the control interface ismountable. For example, the control interface may include a foldable legor other support that permits the control interface to be stood in anear vertical orientation on the top of the housing.

In another embodiment, the enclosure may include an electronics sectionthat is separated and insulated from a disinfection section that isheated to disinfect components of the hemodialysis unit. For example,the disinfection section may include all of the liquid circuitcomponents, such as valves, pumps, conduits, etc., of the variousportions of the dialysis unit. The electronics section may includemotors, computers or other data processing devices, computer memory,and/or other temperature sensitive electronics or other components. Byisolating the electronics section from the disinfection section (atleast to some degree), components in the electronics section may bespared exposure to the heat or other environmental conditions in thedisinfection section whether during a disinfection operation orotherwise.

In another aspect of the invention, a portable hemodialysis system maybe arranged so that power for the fluid circuit pumps of a dialysis unitmay be provided by a modular power unit, e.g., a unit that can beselectively connected to or disconnected from the dialysis unit. As aresult, failure of a power unit need not necessarily disable the entiredialysis system. Instead, the power unit may be replaced with anotherpower unit, allowing for treatment to continue. For example, a modularassembly for a portable hemodialysis system may include a dialysis unit,e.g., including a housing that contains suitable components forperforming hemodialysis, such as a dialyzer, one or more pumps tocirculate blood through the dialyzer, a source of dialysate, and one ormore pumps to circulate the dialysate through the dialyzer. The housingmay have a front panel at which blood circuit connections and dialysatefluidic connections are located, e.g., where an operator may makepatient blood access connections, connect a reagent supply, and/orconnect a dialyzer. The modular assembly may also include a power unithaving a housing that contains suitable components for providingoperating power to the pumps of the dialysis unit. The power unit may beselectively connected to the dialysis unit and provide power to thedialysis unit for the pumps when connected to the dialysis unit, but maybe incapable of providing power to the dialysis unit when disconnectedfrom the dialysis unit. The power unit may be selectively connected toand disconnected from the dialysis unit by operation of a single handle,e.g., an operator may turn or otherwise operate a single handle todisconnect the power unit from the dialysis unit. In one embodiment, thedialysis unit and the power unit are sized and weighted to each becarried by hand by a human.

In one embodiment, the pumps of the dialysis unit are pneumatic pumpsand the power unit provides pneumatic power to the dialysis unit. Forexample, the power unit may provide air pressure and/or vacuum to thedialysis unit to power the pumps. The power unit may include one or moreair pressure pumps and/or air vacuum pumps, and the dialysis unit mayinclude a plurality of valves to control application of pneumatic powerto the pumps. To aid with use of the hemodialysis system in the home,the power unit and dialysis unit electrical power requirements may beprovided by standard residential electrical power, e.g., approximately110V, 15 amp electrical power. The dialysis unit may provide electricalpower to the power unit, and the power unit may use the electrical powerto generate operating power for the pumps.

In another aspect of the invention, a blood circuit assembly for adialysis unit may be arranged to allow the replacement of most or allblood circuit components in a single operation. For example, the bloodcircuit assembly may include an organizing tray, a pair of pneumaticpumps mounted to the organizing tray for circulating blood received froma patient through a circuit including a dialyzer unit and returned tothe patient, an air trap mounted to the organizing tray arranged toremove air from blood circulating in the circuit, a pair of dialyzerconnections arranged to connect to the inlet and outlet of a dialyzerunit, and a pair of blood line connectors, one inlet blood lineconnector for receiving blood from the patient and providing blood tothe pneumatic pumps and the other outlet blood line connector forreturning blood to the patient.

In one embodiment, an anticoagulant connection is provided for engagingwith an anticoagulant source and providing anticoagulant into the bloodcircuit. For example, the anticoagulant connection may include a pumpfor pumping anticoagulant from the anticoagulant source, such as heparinfrom a vial of heparin, to the circuit. The anticoagulant connection mayinclude a vial holder arranged to hold two or more differently sizedvials, and a spike to pierce the vial. In one embodiment, the pair ofpneumatic pumps, the anticoagulant connection, and the anticoagulantpump are part of a pump cassette.

In another embodiment, the blood circuit assembly may be selectivelymounted to and removed from a dialysis unit. To aid in handling of theblood circuit assembly, the organizing tray may include a pair ofhandles arranged for gripping by a user. The organizing tray may alsoinclude openings adjacent each of the handles for receiving retainingtabs on a dialysis unit that engage with the blood circuit assembly andretain the blood circuit assembly on the dialysis unit.

In one embodiment, the inlet blood line connector is connected to aninlet for the pump cassette, an outlet for the pump cassette isconnected to a dialyzer inlet connector, a dialyzer outlet connector isconnected to an inlet of the air trap, and an outlet of the air trap isconnected to the outlet blood line connector. The inlet of the air trapmay be located above the outlet of the air trap when the blood circuitassembly is mounted to a dialysis unit, e.g., to aid in trapping of aircirculating in the circuit during treatment. The blood line connectorsmay be arranged for a threaded luer-type connection to a patient access,as well as be arranged for a press-in type connection to the dialysisunit. Such an arrangement may make it easier for an operator to connectthe blood line connectors to the dialysis unit after treatment (e.g.,for later disinfection and/or priming of the blood circuit) whileallowing the connectors to engage with standard luer-type connectors ata patient blood access.

In one embodiment, the organizing tray may include circuit tubeengagement members having a hole or slot through which a respectivecircuit tube passes. The engagement members may engage with therespective circuit tube to allow the circuit tube to be pulled andstretched for engagement with an occluder of the dialysis unit. Forexample, the circuit tubes of the blood circuit assembly may includesilicone tubing that has to be stretched (and thereby reduced indiameter) to engage with an occluder. The circuit tube engagementmembers may resist the pull of an operator on the tubes, allowing thetubes to be stretched and placed in engagement with the occluder.

In another aspect of the invention, a method for replacing a bloodcircuit assembly of a dialysis unit includes grasping a pair of handleson an organizing tray of a blood circuit assembly that is mounted to adialysis unit, disengaging locking tabs of the dialysis unit from theblood circuit assembly to free the blood circuit assembly from thedialysis unit, and pulling on the handles on the organizing tray of theblood circuit assembly to remove the blood circuit assembly from thedialysis unit. Disengagement of the locking tabs may be performed byflexing the locking tabs away from each other such that each locking tabis moved toward a nearest one of the handles. After removal of the bloodcircuit assembly, a replacement blood circuit assembly may be provided,openings in the organizing tray of the replacement blood circuitassembly may be aligned with the locking tabs so that each locking tabis received into a respective opening, and the organizing tray may bepushed relative to the dialysis unit such that the locking tabs engagewith the replacement blood circuit assembly to mount the replacementblood circuit assembly to the dialysis unit. Mounting the replacementblood circuit assembly may also involve connecting control ports on thedialysis unit to mating ports on the assembly so that fluid controlsignals may be provided for pumps and valves of the blood circuitassembly. Other blood circuit connections may be made, such as inlet andoutlet connections for the dialyzer, and the blood line connectors maybe connected to receive dialysate into the blood circuit.

In another aspect of the invention, an air trap for a blood circuit in adialysis unit includes a blood inlet supply line, a blood outlet supplyline, and a container having an approximately spherical internal wall,an inlet at a top end of the container connected to the blood inletsupply line, and an outlet at a bottom end of the container connected tothe blood outlet supply line. The inlet may be offset from a verticalaxis of the approximately spherical internal wall such that bloodentering the container through the inlet is directed to flow in aroundthe approximately spherical wall in a spiral-like path. Such flow in thecontainer may help to remove air bubbles from the blood as it flows fromthe inlet to the outlet, with any removed air remaining near the top ofthe container. The inlet port may be arranged to introduce blood intothe container in a direction that is approximately tangential to theapproximately spherical inner wall of the container and/or in adirection that is approximately perpendicular to the vertical axis ofthe container.

In one embodiment, a self-sealing port may be located at a top of thecontainer, e.g., in the form of a split septum that is arranged topermit introduction of fluid into, and withdrawal of liquid from, thecontainer by inserting a needleless device through the split septum. Theself-sealing port may be arranged to be self-cleaning when disinfectionliquid is circulated through the container, e.g., the port may besuitably exposed to flowing disinfection liquid to remove debris and/orheat material on the port to achieve desired disinfection.

In another aspect of the invention, a tube securing arrangement of ablood circuit assembly includes a organizing tray that supportscomponents of a blood circuit assembly and includes a pair of tubeengagement members each having a hole, a pair of patient inlet andoutlet lines arranged to connect with patient access points forreceiving liquid from and/or providing liquid to the patient, and a pairof stops on the patient inlet and outlet lines, respectively. Thepatient inlet and outlet lines may each pass through a hole of arespective tube engagement member so that the stop engages with the tubeengagement member. With this arrangement, the tube engagement membersmay resist pulling and stretching of the inlet and outlet lines whenengaging the lines with an occluder. The tube engagement members may beflexible to allow a user to press inwardly on the engagement member andseat the respective inlet or outlet line in the occluder, yet resistdownward pulling of the line.

In another aspect of the invention, a hemodialysis system includes adialyzer mount arranged to support a plurality of differently sizedand/or shaped dialyzer units and to accommodate different distancesbetween dialysate connections on the dialyzer units. The dialyzer mount,which may be located on a front panel of the dialysis unit, may includea pair of flange portions that are each arranged to engage with arespective dialysate quick-connect fitting connected to a dialysate portof the dialyzer. Each flange portion may be arranged to engage with agroove on the quick connect fitting that is located between a portion ofthe base of the quick connect fitting and a slide element of the quickconnect fitting. For example, the dialyzer mount may include a pair ofkeyhole features with each keyhole feature having an upper insertionarea sized to receive a portion of the base of the quick-connect fittinginserted into the upper insertion area, and a lower flanged portionhaving a width that is smaller than an overall a width of the base ofthe quick-connect fitting and that engages with a groove on the quickconnect fitting. The lower flanged portion may include a pair ofopposite flanges that engage with the groove and allow the quick-connectfitting to slide along the flanges.

In one embodiment, the bottom keyhole feature may include an adjustablesupport that is moveable in a vertical direction. For example, theadjustable support may be movable along the opposed flanges. Thus, theadjustable support may be fixable in a plurality of different positionson the flanges to support the weight of the dialyzer. In onearrangement, the adjustable support includes a “U” shaped member and atleast one thumb screw that may be tightened to fix the “U” shaped memberin place.

In another aspect of the invention, a blood line connector for a bloodcircuit of a hemodialysis unit may have the ability to make twodifferent types of fluid tight connections, e.g., a screw-typeconnection with a luer connector at a patient access and a press-in typeconnection with a dialysate circuit of the hemodialysis unit. Forexample, the blood line connector may include a tube connection endarranged to sealingly engage with a blood circuit tube, and a patientaccess connection end with a frustoconical member having an internallythreaded portion arranged to engage with an externally threaded patientaccess, and a pair of locking arms extending rearwardly from thefrustoconical member. The locking arms may each have a finger depressionportion and a barbed portion, and may be arranged to engage with amating connector on the dialysis unit at the barbed portions to lock thefrustoconical member in sealing engagement with the mating connectorwhen making a press-in type connection. The barbed portions maydisengage from the mating connector when the finger depression portionsare urged toward each other. In one embodiment, the patient accessconnection end may include a central tube extending from the center ofthe frustoconical member. The internally threaded portion of thefrustoconical member and the central tube may be arranged to mate with afemale luer-type patient access connector or any other suitablescrew-type connection.

In another aspect of the invention, a method for operating a dialysisunit includes connecting blood line connectors of arterial and venousblood lines for a dialysis unit to patient access connectors incommunication with a patient blood system. In one embodiment, thepatient access connectors may require a corresponding blood lineconnector to establish a threaded engagement with the patient accessconnector, thereby forming a luer or screw-type connection between theblood line connectors and the patient access connectors. The dialysisunit may be operated to withdraw blood from a patient access connectorand into an arterial blood line, subject the withdrawn blood to adialysis process to produce treated blood, and return the treated bloodto the patient via the venous blood line and the other patient accessconnector. Thereafter, the blood line connectors may be disconnectedfrom the patient access connectors by unscrewing the blood lineconnectors from a corresponding patient access connector, and the bloodline connectors may be connected to a directing circuit of the dialysisunit. The blood line connectors may be connected to the directingcircuit by a press-in connection with a corresponding connection pointon the dialysis unit, e.g., by pushing the blood line connectors intothe connection points to establish the press-in connection.

In another aspect of the invention, a reagent supply arrangement for ahemodialysis system may be arranged to provide two or more reagentmaterials for use in preparing a dialysate and may include a connectorarranged to help prevent the connection of a reagent material to thewrong port. For example, the reagent supply may include an E-prongconnector having three parallel prongs with two outer prongs arranged ina common plane and a center prong arranged above the common plane, afirst supply line for a first reagent connected in fluid communicationwith one of the outer prongs, a second supply line for a second reagentconnected in fluid communication with the other of the outer prongs, aliquid line connected in fluid communication with the center prong, anda container for housing the first reagent having an inlet connected tothe liquid line and an outlet connected to the first supply line for thefirst reagent. The E-prong connector may help prevent the improperconnection of the first and second supply lines to the dialysis unit,e.g., because the central prong being located out of the plane of thetwo outer prongs ensure connection of the E-prong connector in only oneway to the dialysis unit.

In one embodiment, the container includes a bicarbonate materialsuitable for use in generating a dialysate for the hemodialysis system.The liquid line may be a water supply line that provides water to thecontainer, allowing the water to mix with the bicarbonate (which may bein powder or other solid form) and flow to the first supply line. Thesecond supply line may be an acid supply line that includes a connectorand provides acid material to the E-prong connector. The reagent supplymay also include an acid bag spike that is removably engaged with theconnector of the acid supply line. The acid bag spike may include aspike member and a pair of spring clips at an end of the acid bag spikeopposite the connector of the acid supply line, allowing the acid bagspike to be fluidly connected with an acid bag or other acid source.

In another aspect of the invention, a method for operating ahemodialysis system includes providing a dialysis unit having anenclosure containing suitable components for performing hemodialysisincluding a dialyzer, one or more pumps to circulate blood through thedialyzer, a source of dialysate, and one or more pumps to circulate thedialysate through the dialyzer. The enclosure may include a housing thatsupports the components and has a front panel at which blood circuitconnections and dialysate fluidic connections are made. A reagent supplymay be provided including an E-prong connector, a first supply line fora first reagent connected in fluid communication with one of the outerprongs, a second supply line for a second reagent connected in fluidcommunication with the other of the outer prongs, a liquid lineconnected in fluid communication with the center prong, and a containerfor housing the first reagent having an inlet connected to the liquidline and an outlet connected to the first supply line for the firstreagent. The E-prong connector may be engaged with a connection point atthe front panel of the dialysis unit, thereby allowing the dialysis unitto provide water to the liquid line of the reagent supply, and allowingthe dialysis unit to receive the first and second reagents from thefirst and second supply lines.

Other advantages and novel features of the present invention will becomeapparent from the following detailed description of various non-limitingembodiments of the invention when considered in conjunction with theaccompanying figures. In cases where the present specification and adocument incorporated by reference include conflicting and/orinconsistent disclosure, the present specification shall control. If twoor more documents incorporated by reference include conflicting and/orinconsistent disclosure with respect to each other, then the documenthaving the later effective date shall control.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects of the invention are described with reference to illustrativeembodiments, which are described with reference to the drawings in whichlike numerals reference like elements, and wherein:

FIG. 1 is a schematic representation of fluid handling components of ahemodialysis system in an illustrative embodiment;

FIG. 2 shows a schematic fluid flow diagram for the dialysis system ofFIG. 1;

FIG. 3 is a schematic fluid flow diagram for the blood flow circuit ofthe FIG. 2 embodiment;

FIG. 4 is a schematic fluid flow diagram for the balancing circuit ofthe FIG. 2 embodiment;

FIG. 5 is a schematic fluid flow diagram for the directing circuit ofthe FIG. 2 embodiment;

FIG. 5A is a schematic fluid flow diagram illustrating a flow path for adrain assembly in an illustrative embodiment;

FIG. 6 is a schematic fluid flow diagram for the mixing circuit of theFIG. 2 embodiment;

FIG. 7 is a right front perspective view of a hemodialysis system in anillustrative embodiment;

FIG. 7a is perspective view of selected components of a power unit in anillustrative embodiment;

FIG. 7b is a schematic view of an air dehumidifier arrangement in anillustrative embodiment;

FIG. 7c is a perspective view of a dehumidifier arrangement in the FIG.7a embodiment;

FIG. 8 is a left rear perspective view of the hemodialysis system ofFIG. 7;

FIG. 9 is a front view of the hemodialysis system of FIG. 7;

FIG. 10 is a right front perspective view of the view of thehemodialysis system of FIG. 7 with the doors in a first open position;

FIG. 11 is a top view of the hemodialysis system of FIG. 10;

FIG. 12 is a front view of the hemodialysis system of FIG. 10;

FIG. 13 is a right side view of the hemodialysis system of FIG. 10;

FIG. 14 is a right front perspective view of the view of thehemodialysis system of FIG. 7 with the doors in a second open position;

FIG. 15 is a top view of the hemodialysis system of FIG. 14;

FIG. 16 is a front view of the hemodialysis system of FIG. 14;

FIG. 17 is a front view of the hemodialysis system of FIG. 7 with thedoors in an open position exposing a front panel of the system;

FIG. 17a is an exploded perspective view of a control port assemblyarranged to interface with a blood pump assembly in an illustrativeembodiment;

FIG. 17b is a cross sectional side view of the FIG. 17a embodiment withan engaged blood pump assembly;

FIG. 17C shows a perspective view of a control port assembly with a pairof blood pump cassette latching and ejection assemblies in anillustrative embodiment;

FIG. 17D shows an isolated view of a latching assembly with an ejectionmember in a retracted position in an illustrative embodiment;

FIG. 17E shows an isolated view of the latching assembly of FIG. 17Dwith an ejection member in an extended position in an illustrativeembodiment;

FIG. 17F shows a front view of a blood pump cassette in a retainedcondition on a panel of a dialysis unit in an illustrative embodiment;

FIG. 17G shows a cross-sectional view along the line 17G-17G in FIG.17F; FIG. 17H shows a cross-sectional view along the line 17H-17H inFIG. 17F;

FIG. 17I shows a front view of a blood pump cassette in an ejectingcondition in an illustrative embodiment;

FIG. 17J shows a cross-sectional view along the line 17J-17J in FIG.17I;

FIG. 17K shows a cross-sectional view along the line 17K-17K in FIG.17I;

FIG. 18 is a front view of a blood circuit assembly for use with thesystem of FIG. 7;

FIG. 18a is a perspective view of a blood pump having a medicationholder in an illustrative embodiment;

FIG. 19 right perspective view of a organizing tray for the bloodcircuit assembly of FIG. 18;

FIG. 20 is a left rear perspective view of the blood circuit assembly ofFIG. 18;

FIG. 20A is an front exploded view of an alternate embodiment of a bloodpump cassette;

FIG. 20B is a rear exploded view of the blood pump cassette of FIG. 20A;

FIG. 20C is a front view of a bottom plate or back plate of the bloodpump cassette of FIG. 20A;

FIG. 20D is a back view of a bottom plate or back plate of the bloodpump cassette of FIG. 20A;

FIG. 21 shows a left front perspective view of the front panel of thesystem of FIG. 7;

FIG. 21A shows a front view of an alternate embodiment of a front panelassembly in an illustrative embodiment;

FIG. 21B shows the front panel assembly of FIG. 21A with the top andmiddle plate components of the blood pump cassette removed for clarityin an illustrative embodiment;

FIG. 22 shows a front view of the front panel of the system of FIG. 7;

FIG. 23 shows a front view of the front panel of the system of FIG. 7with a pair of mounting features for the dialyzer;

FIG. 24 shows a side view of a dialyzer with quick-connect fittingsattached to the dialysate inlet/outlet ports of the dialyzer;

FIG. 25 shows a right perspective view of a reagent supply for use withthe system of FIG. 7;

FIG. 26 shows a perspective view of an E-prong connector for the reagentsupply of FIG. 25 and a corresponding connection point at the frontpanel of the hemodialysis system;

FIG. 27 shows a perspective view of a pair of blood line connectors forthe blood circuit assembly and a corresponding connection point at thefront panel of the hemodialysis system;

FIG. 28 shows a side view of a blood line connector and connection pointof FIG. 27

FIG. 29 is a perspective view of a blood circuit assembly in analternate embodiment; and

FIG. 30 is a close up view of a portion of the blood circuit assembly ofFIG. 29.

FIG. 31 shows an exemplary modular drain cassette in an illustrativeembodiment;

FIG. 32 shows the drain cassette of FIG. 31 in an exploded view with anescutcheon positioned anterior to a front wall of the drain cassette inan illustrative embodiment;

FIG. 33 shows a perspective view of the front wall of the drain cassetteof FIG. 31 in an illustrative embodiment;

FIG. 34 shows a main housing of the drain cassette of FIG. 31 with thefront wall removed for clarity purposes in an illustrative embodiment;

FIG. 35 shows a rear, perspective view of the drain cassette of FIG. 31in an illustrative embodiment;

FIG. 36 shows a front panel in which a drain cassette has beendismounted in an illustrative embodiment;

FIG. 37 is a schematic representation of a conductivity circuit in anillustrative embodiment;

FIG. 38 is a diagram of the electrical waveforms processed by thecircuit of FIG. 37;

FIG. 39 is a representative graph of the noise/error sensitivity of thecircuit of FIG. 37 plotted against the ratio of unknown/referenceresistance in the circuit;

FIG. 40 is a schematic representation of an exemplary blood flow circuitof a hemodialysis system;

FIG. 41A is a side view of a connector that may be used in the bloodflow circuit of FIG. 4;

FIG. 41B is a cross-sectional view of the connector of FIG. 41A;

FIG. 42 is a cross-sectional view of the connector of FIGS. 41A and 41B,with an attached wire and flexible tubing;

FIG. 43A is a perspective view of an alternate embodiment of a connectorthat may be used in the blood flow circuit of FIG. 40;

FIG. 43B is a top view of the connector of FIG. 43A;

FIG. 43C is a cross-sectional view of the connector of FIG. 43B;

FIGS. 44A-D are various cross-sectional views of a flexible tubeincorporating a conductive wire;

FIG. 45 is a perspective view of a flexible double-lumen tube having afluid-carrying lumen and a wire-carrying lumen;

FIG. 46 is a cross-sectional view of a connector similar to theconnector of FIGS. 43A-C, with an attached wire and tubing;

FIG. 47 is a plan view of an extracorporeal blood flow circuit used in arepresentative hemodialysis system;

FIG. 48 is a perspective view of a hemodialysis apparatus configured toreceive and operate the extracorporeal blood flow circuit of FIG. 47;and

FIG. 49 is a representative plot of the resistance measured by theconductivity circuit of FIG. 37 under various conditions;

FIG. 50 shows an exploded, perspective view of an occlusion assemblyfrom a front angle in accordance with an embodiment of the presentdisclosure;

FIG. 51 shows an exploded, perspective view of the occlusion assembly ofFIG. 1 from a back angle;

FIG. 52 shows a front, perspective view of the occlusion assembly ofFIG. 1 with the door open and the button pressed to illustrate loadingof a tube;

FIG. 53 shows a close-up perspective view of the occlusion assembly ofFIG. 1, showing the door engaging a switch when the door is closed;

FIG. 54 shows the front of the occlusion assembly of FIG. 1 without thedoor and frame to illustrate the arms fully occluding flexible tubes;

FIG. 55 shows the front of the occlusion assembly of FIG. 1 without thedoor and frame to illustrate the arms in a non-occluding position;

FIG. 56 is a rear/top perspective view of the occlusion assembly of FIG.1 with an actuator arm in a fully retracted position;

FIG. 57 is a rear perspective view of the occlusion assembly of FIG. 1with an actuator arm in a fully extended position;

FIG. 58 shows a side perspective view of several working parts of theocclusion assembly of FIG. 1 in a non-occluding state;

FIG. 59 shows a side perspective view of several working parts of theocclusion assembly of FIG. 1 in an occluding state;

FIG. 60 shows a side, cross-sectional view of an actuator of theocclusion assembly of FIG. 1, illustrating a location for a main springfor the assembly; and

FIG. 61 shows the occlusion assembly of FIG. 50 mounted in a front panelassembly of a hemodialysis apparatus in accordance with an embodiment ofthe present disclosure.

DETAILED DESCRIPTION

Various aspects of the invention are generally directed to new systemsfor hemodialysis and the like, such as hemofiltration systems,hemodiafiltration systems, plasmapheresis systems, etc. Accordingly,although the various systems and methods described herein are describedin relation to hemodialysis, it should be understood that the varioussystems and method described herein are applicable to other dialysissystems and/or in any extracorporeal system able to treat blood or otherbodily fluids, such as plasma.

As discussed below, a hemodialysis system typically includes a bloodflow path and a dialysate flow path. It should be noted that within suchflow paths, the flow of fluid is not necessarily linear, and there maybe any number of “branches” within the flow path that a fluid can flowfrom an inlet of the flow path to an outlet of the flow path. Examplesof such branching are discussed in detail below. In the blood flow path,blood is drawn from a patient, and is passed through a dialyzer, beforebeing returned to the patient. The blood is treated by the dialyzer, andwaste molecules (e.g., urea, creatinine, etc.) and water are passed fromthe blood, through a semi-permeable membrane in the dialyzer, into adialysate solution that passes through the dialyzer by the dialysateflow path. In various embodiments, blood may be drawn from the patientfrom two lines (e.g., an arterial line and a venous line, i.e., “dualneedle” flow), or in some cases, blood may be drawn from the patient andreturned through the same or catheter needle (e.g., the two lines orlumens may both be present within the same needle, i.e., a form of “duallumen” flow). In still other embodiments, a “Y” site or “T” site isused, where blood is drawn from the patient and returned to the patientthrough one patient connection having two branches (one being the fluidpath for the drawn blood, the second the fluid path for the returnblood, i.e., a form of “single needle” flow). The patient may be anysubject in need of hemodialysis or similar treatments, includingnon-human subjects, such as dogs, cats, monkeys, and the like, as wellas humans.

In the dialysate flow path, fresh dialysate is prepared and is passedthrough the dialyzer to treat the blood from the blood flow path. Thedialysate may also be equalized for blood treatment within the dialyzer(i.e., the pressure between the dialysate and the blood are equalized),often exactly, or in some embodiments, at least within about 1% or about2% of the pressure of the blood. In some cases, it may be desirable tomaintain a greater pressure difference (either positive or negative)between the blood flow path and dialysate flow path. After passingthrough the dialyzer, the used dialysate, containing waste molecules (asdiscussed below), is discarded in some fashion. The dialysate in somecases may be re-circulated in a “multi-pass” arrangement, which may bebeneficial in capturing larger molecules having low mobility across thedialyzer. In some cases, the dialysate is heated prior to treatment ofthe blood within the dialyzer using an appropriate heater, such as anelectrical resistive heater. The dialysate may also be filtered toremove contaminants, infectious organisms, debris, and the like, forinstance, using an ultrafilter. The ultrafilter may have a pore sizechosen to prevent species such as these from passing therethrough. Forinstance, the pore size may be less than about 0.3 micrometers, lessthan about 0.2 micrometers, less than about 0.1 micrometers, or lessthan about 0.05 micrometers, etc. The dialysate is used to draw wastemolecules (e.g., urea, creatinine, ions such as potassium, phosphate,etc.) and water from the blood into the dialysate through osmosis orconvective transport, and dialysate solutions are well-known to those ofordinary skill in the art.

The dialysate typically contains various ions such as sodium, chloride,bicarbonate, potassium and calcium that are similar in concentration tothat of normal blood. In some cases, the bicarbonate, may be at aconcentration somewhat higher than found in normal blood. Typically, thedialysate is prepared by mixing water from a water supply with one ormore ingredients: an “acid” (which may contain various species such asacetic acid, dextrose, NaCl, CaCl, KCl, MgCl, etc.), sodium bicarbonate(NaHCO₃), and/or sodium chloride (NaCl). The preparation of dialysate,including using the appropriate concentrations of salts, osmolarity, pH,and the like, is well-known to those of ordinary skill in the art. Asdiscussed in detail below, the dialysate need not be prepared at thesame rate that the dialysate is used to treat the blood. For instance,the dialysate can be made concurrently or prior to dialysis, and storedwithin a dialysate storage vessel or the like.

Within the dialyzer, the dialysate and the blood typically are separatedby a semi-permeable membrane. Typically, the semipermeable membrane isformed from a polymer such as cellulose, polyarylethersulfone,polyamide, polyvinylpyrrolidone, polycarbonate, polyacrylonitrile, orthe like, which allows the transport of ions or small molecules (e.g.,urea, water, etc.), but does not allow bulk transport or convectionduring treatment of the blood. In some cases (such as high-fluxdialyzers), even larger molecules, such as beta-2-microglobulin, maypass through the membrane. In some cases, for example, ions andmolecules may pass through the dialyzer by convective flow if ahydrostatic pressure difference exists across the semi-permeablemembrane.

It should be noted that, as used herein, “fluid” means anything havingfluidic properties, including but not limited to, gases such as air, andliquids such as water, aqueous solution, blood, dialysate, etc.

FIG. 1 shows a schematic block diagram of fluid circuitry for ahemodialysis system that incorporates various aspects of the invention.In this illustrative embodiment, the dialysis system 5 includes a bloodflow circuit 141 that draws blood from a patient, passes the bloodthrough a dialyzer 14, and returns the treated blood to the patient. Abalancing circuit or an internal dialysate circuit 143 receivesdialysate from an ultrafilter 73, passes the dialysate through thedialyzer 14, and receives used dialysate from the dialyzer 14. Adirecting circuit or an external dialysate circuit 142 provides freshdialysate to the ultrafilter 73, and receives used dialysate from theinternal dialysate circuit 143 (which may be directed to a drain 31).The directing circuit 142 can also receive water from a water supply 30and pass it to a mixing circuit 25. The mixing circuit 25 formsdialysate using water from the directing circuit 142 and reagentingredients 49, such as citric acid, salt and a bicarbonate, that may bereceived from a renewable source. The mixing circuit 25 may preparedialysate, for example, on an as-needed basis, during and/or in advanceof dialysis. New dialysate prepared by the mixing circuit 25 may beprovided to the directing circuit 142, which may provide the dialysateto the ultrafilter 73, as described above. The directing circuit 142 mayinclude a heater to heat the dialysate to a suitable temperature and/orto heat fluid in the system for disinfection. Conduits 67 (shown indotted line) may be connected between the blood flow circuit 141 and thedirecting circuit 142, e.g., for disinfection of the hemodialysissystem.

FIG. 2 is a schematic diagram showing a more detailed circuitarrangement for the dialysis system 5 shown in FIG. 1. It should beunderstood, of course, that FIG. 2 is only one possible embodiment ofthe general hemodialysis system of FIG. 1, and in other embodiments,other fluid circuits, modules, flow paths, layouts, etc. are possible.Examples of such systems are discussed in more detail below, and alsocan be found in the following, each of which is incorporated herein byreference: U.S. application Ser. No. 12/072,908, filed Feb. 27, 2008,U.S. Provisional Application 60/903,582, filed Feb. 27, 2007, U.S.Provisional Application 60/904,024, filed Feb. 27, 2007, U.S. patentapplication Ser. No. 11/871,680, filed Oct. 12, 2007, U.S. patentapplication Ser. No. 11/871,712, filed Oct. 12, 2007, U.S. patentapplication Ser. No. 11/871,787, filed Oct. 12, 2007, U.S. patentapplication Ser. No. 11/871,793, filed Oct. 12, 2007, or U.S. patentapplication Ser. No. 11/871,803, filed Oct. 12, 2007.

The blood flow circuit 141 includes an anticoagulant supply 11 and ablood flow pump 13 which pumps blood from a patient through a dialyzer14 and returns the blood to the patient. The anticoagulant supply 11,although shown in the path of blood flowing towards the dialyzer, may beinstead located in another suitable location. e.g., any locationupstream or downstream from blood flow pump 13. The balancing circuit143 includes two dialysate pumps 15, which pump dialysate into thedialyzer 14, and a bypass pump 35. The flow of blood through the bloodflow circuit 141 in some cases, is synchronized with the flow ofdialysate in the dialysate flow path. In an embodiment, the flow ofdialysate into and out of the dialyzer 14 and the balancing circuit 143is balanced volumewise using balancing chambers in the balancing circuit143. The directing circuit 142 includes a dialysate pump 159, whichpumps dialysate from a dialysate tank 169 through a heater 72 and/or theultrafilter 73 to the balancing circuit 143. The directing circuit 142also receives waste fluid from balancing circuit 143 and directs it to adrain 31. In some cases, the blood flow circuit 141 can be connected viaconduits 67 to the directing circuit 142, e.g., for disinfection, asdiscussed below. Dialysate in the dialysate tank 169 is provided by themixing circuit 25, which produces the dialysate using water from a watersupply 30 provided via the directing circuit 142 and dialysateingredients 49 (e.g., bicarbonate and acid). A series of mixing pumps180, 183, 184 are used to mix the various components and produce thedialysate.

FIG. 3 shows a close-up view of the blood flow circuit 141 in thisillustrative embodiment. Under normal operation, blood flows from apatient through arterial line 203 via blood flow pump 13 to the dialyzer14 (the direction of flow during normal dialysis is indicated by arrows205; in some modes of operation, however, the flow may be in differentdirections, as discussed below). Optionally, an anticoagulant may beintroduced into the blood via anticoagulant pump 80 from ananticoagulant supply. After passing through dialyzer 14 and undergoingdialysis, the blood returns to the patient through venous line 204,optionally passing through an air trap and/or a blood sample port 19.The pump 13 may include, for instance, pumps 23 that are actuated by acontrol fluid.

For example, in one embodiment, the blood flow pump 13 may comprise two(or more) pod pumps 23. Each pod pump, in this particular example, mayinclude a rigid chamber with a flexible diaphragm or membrane dividingeach chamber into a pumping compartment and control compartment. Theremay be four entry/exit valves for these compartments, two for thepumping compartment and two for the control compartment. The valves forthe control compartment of the chambers may be two-way proportionalvalves, one connected to a first control fluid source (e.g., a highpressure air source), and the other connected to a second control fluidsource (e.g., a low pressure air source) or a vacuum source. The fluidvalves can be opened and closed to direct fluid flow when the pod pumps23 are operating. Non-limiting examples of pod pumps are described inU.S. Provisional Application 60/792,073, filed Apr. 14, 2006, or in U.S.patent application Ser. No. 11/787,212, filed Apr. 13, 2007, eachincorporated herein by reference. If more than one pod pump is present,the pod pumps may be operated in any suitable fashion, e.g.,synchronously, asynchronously, in-phase, out-of-phase, etc. Forinstance, in some embodiments, the two-pump pumps can be cycled out ofphase to affect the pumping cycle, e.g., one pump chamber fills whilethe second pump chamber empties. A phase relationship anywhere between0° (the pod pumps fill and empty in unison) and 180° (one pod pump fillsas the other empties) can be selected in order to impart any desiredpumping cycle. A phase relationship of 180° may yield continuous flowinto and out of the set of pod pumps. This is useful, for instance, whencontinuous flow is desired, e.g., for use with dual needle or dual lumencatheter flow. Setting a phase relationship of 0°, however, may beuseful in some cases for single needle/single lumen flow or in othercases. In a 0° relationship, the pod pumps will first fill from theneedle, then deliver blood through the blood flow path and back to thepatient using the same needle. In addition, running at phases between 0°and 180° can be used in some cases, to achieve a push/pull relationship(hemodiafiltration or continuous back flush) across the dialyzer.

An anticoagulant (e.g., heparin, or any other suitable anticoagulant)may be contained within a vial 11 (or other anticoagulant supply, suchas a tube or a bag), and blood flow circuit 141 may include a spike 201(which, in one embodiment, is a needle) that can pierce the seal of thevial. The spike 201 may be formed from plastic, stainless steel, oranother suitable material, and may be a sterilizable material in somecases, e.g., the material may be able to withstand sufficiently hightemperatures and/or radiation so as to sterilize the material.

An anticoagulant pump 80, which can act as a metering chamber in somecases, can be used to control the flow of anticoagulant into the bloodcircuit. The anticoagulant pump 80 may be a pod pump or a membrane-basedmetering pump, and/or may be actuated by a control fluid, such as air.For example, the anticoagulant pump 80 may include a rigid chamber witha flexible diaphragm dividing the chamber into a pumping compartment anda control compartment. One valve for the control compartment of thechamber may be connected to a first control fluid source (e.g., a highpressure air source), and the other valve connected to a second controlfluid source (e.g., a low pressure air source) or a vacuum source.Valves for the pumping compartment of the chamber can be opened andclosed in coordination with the control compartment, thus controllingthe flow of anticoagulant into the blood. In one set of embodiments, airprovided through a filter 81 may also be introduced into the blood flowpath by the anticoagulant pump 80, e.g., to provide air into the vial 11after or before anticoagulant is withdrawn from the vial.

Fluid Management System (“FMS”) measurements may be used to measure thevolume of fluid pumped through a pump chamber during a stroke of themembrane, or to detect air in the pumping chamber. FMS methods aredescribed in U.S. Pat. Nos. 4,808,161; 4,826,482; 4,976,162; 5,088,515;and 5,350,357, which are hereby incorporated herein by reference intheir entireties. In one illustrative embodiment, the volume of liquiddelivered by an anticoagulant pump, a dialysate pump, or othermembrane-based fluid pump is determined using an FMS algorithm in whichchanges in chamber pressure are used to calculate a volume measurementat the end of a fill stroke and at the end of a delivery stroke. Thedifference between the computed volumes at the end of fill and deliverystrokes may be used to determine the actual stroke volume. This actualstroke volume can be compared to an expected stroke volume for theparticular sized chamber. If the actual and expected volumes aresignificantly different, the stroke has not properly completed and anerror message can be generated.

The blood flow circuit 141 may also include an air trap 19 to remove airbubbles that may be present within the blood flow path. In some cases,the air trap 19 is able to separate any air that may be present from theblood due to gravity, and/or may include a port for sampling blood.

FIG. 4 shows a close-up view of the balancing circuit 143 in the FIG. 2embodiment. In the balancing circuit 143, dialysate flows from theoptional ultrafilter 73 into a dialysate pump 15. In this embodiment,the dialysate pump 15 includes two pod pumps 161, 162, two balancingchambers 341, 342, and a pump 35 for bypassing the balancing chambers341, 342. The balancing chambers 341, 342 may be constructed such thatthey are formed from a rigid chamber with a flexible diaphragm dividingthe chamber into two separate fluid compartments, so that entry of fluidinto one compartment can be used to force fluid out of the othercompartment and vice versa. Non-limiting examples of pumps that can beused as pod pumps and/or balancing chambers are described in U.S.Provisional Application 60/792,073, filed Apr. 14, 2006, or in U.S.patent application Ser. No. 11/787,212, filed Apr. 13, 2007.

In one embodiment, balancing of flow in the internal dialysate circuitworks as follows. A set of pneumatically operated valves 211, 212, 213,241, 242 has its operation synchronized and controlled together, wherevalves 211, 212, 213 are ganged and valves 241 and 242 are ganged, and asecond set of pneumatically operated valves 221, 222, 223, 231, 232similarly have its operation synchronized and controlled together, wherevalves 221, 222, 223 are ganged, and valves 231 and 232 are ganged. At afirst point of time, the first set of valves 211, 212, 213, 241, 242 isopened while the second set of valves 221, 222, 223, 231, 232 is closed.Fresh dialysate flows into balancing chamber 341 while used dialysateflows from dialyzer 14 into pod pump 161. Fresh dialysate does not flowinto balancing chamber 342 since valve 221 is closed. As fresh dialysateflows into balancing chamber 341, used dialysate within balancingchamber 341 is forced out and exits balancing circuit 143 (the useddialysate cannot enter pod pump 161 since valve 223 is closed).Simultaneously, pod pump 162 forces used dialysate present within thepod pump into balancing chamber 342 (through valve 213, which is open;valves 242 and 222 are closed, ensuring that the used dialysate flowsinto balancing chamber 342). This causes fresh dialysate containedwithin balancing chamber 342 to exit the balancing circuit 143 intodialyzer 14. Also, pod pump 161 draws in used dialysate from dialyzer 14into pod pump 161.

Once pod pump 161 and balancing chamber 341 have filled with dialysate,the first set of valves 211, 212, 213, 241, 242 is closed and the secondset of valves 221, 222, 223, 231, 232 is opened. Fresh dialysate flowsinto balancing chamber 342 instead of balancing chamber 341, as valve212 is closed while valve 221 is now open. As fresh dialysate flows intobalancing chamber 342, used dialysate within the chamber is forced outand exits balancing circuit, since valve 213 is now closed. Also, podpump 162 now draws used dialysate from the dialyzer into the pod pump,while used dialysate is prevented from flowing into pod pump 161 asvalve 232 is now closed and valve 222 is now open. Pod pump 161 forcesused dialysate contained within the pod pump (from the previous step)into balancing chamber 341, since valves 232 and 211 are closed andvalve 223 is open. This causes fresh dialysate contained withinbalancing chamber 341 to be directed into the dialyzer 14 (since valve241 is now open while valve 212 is now closed). At the end of this step,pod pump 162 and balancing chamber 342 have filled with dialysate. Thisputs the state of the system back into the configuration at thebeginning of this description, and the cycle is thus able to repeat,ensuring a constant flow of dialysate to and from the dialyzer 14. In anembodiment, the fluid (e.g. pneumatic) pressures on the control side ofthe balancing chamber valves are monitored to ensure they arefunctioning (e.g., opening and closing) properly.

As a specific example, a vacuum (e.g., 4 p.s.i. of vacuum) can beapplied to the port for the first set of valves, causing those valves toopen, while positive pressure (e.g., 20 p.s.i. of air pressure) isapplied to the second set of valves, causing those valves to close (orvice versa). The pod pumps each urge dialysate into one of the volumesin one of the balancing chambers 341, 342. By forcing dialysate into avolume of a balancing chamber, an equal amount of dialysate is squeezedby the diaphragm out of the other volume in the balancing chamber. Ineach balancing chamber, one volume is occupied by fresh dialysateheading towards the dialyzer and the other volume is occupied by useddialysate heading from the dialyzer. Thus, the volumes of dialysateentering and leaving the dialyzer are kept substantially equal.

The bypass pump 35 can direct the flow of dialysate from the dialyzer 14through balancing circuit 143 without passing through either of podpumps 161 or 162. In this embodiment, the bypass pump 35 is a pod pump,similar to those described above, with a rigid chamber and a flexiblediaphragm dividing each chamber into a fluid compartment and a controlcompartment. This pump may be the same or different from the other podpumps and/or metering pumps described above. When control fluid is usedto actuate the bypass pump 35, the additional drop in pressure on theexiting (spent) dialysate side of the dialyzer causes additionalultrafiltration of fluid from the blood in the dialyzer. This may causea net efflux of fluid from the patient's blood, through the dialyzer,and ultimately to drain. Such a bypass may be useful, for example, inreducing the amount of fluid a patient has, which is often increased dueto the patient's inability to excrete excess fluid (primarily water)through the kidneys. As shown in FIG. 4, the bypass pump 35 may becontrolled by a control fluid (e.g., air), irrespective of the operationof pod pumps 161 and 162. This configuration may allow for easiercontrol of net fluid removal from a patient, without having to operatethe inside dialysate pumps either out of balance or out of phase withthe blood pumps in order to achieve such fluid withdrawal from thepatient.

To achieve balanced flow across the dialyzer, the blood flow pump, thepumps of the balancing circuit, and the pumps of the directing circuit(discussed below) may be operated to work together to ensure that flowinto the dialyzer is generally equal to flow out of the dialyzer. Ifultrafiltration is required, the ultrafiltration pump (if one ispresent) may be run independently of some or all of the other bloodand/or dialysate pumps to achieve the desired ultrafiltration rate.

To prevent outgassing of the dialysate, the pumps of the balancingcircuit may be kept at pressures above atmospheric pressure. Incontrast, however, the blood flow pump and the directing circuit pumpsuse pressures below atmosphere to pull the diaphragm towards the chamberwall to complete a fill stroke. Because of the potential of fluidtransfer across the semi-permeable membrane of the dialyzer and becausethe pumps of the balancing circuit run at positive pressures, thebalancing circuit pumps may be able to use information from the bloodflow pump(s) in order to synchronize the delivery strokes of thebalancing circuit chambers to the dialyzer with the delivery strokes ofthe blood pumps.

In one set of embodiments, when running in such a balanced mode, ifthere is no delivery pressure from the blood flow pump, the balancingcircuit pump diaphragm will push fluid across the dialyzer into theblood and the alternate pod of the balancing circuit will not completelyfill. For this reason, the blood flow pump reports when it is activelydelivering a stroke. When the blood flow pump is delivering a stroke theinside dialysate pump operates. When the blood flow pump is notdelivering blood, the valves that control the flow from the dialyzer tothe inside dialysate pumps (and other balancing valves ganged togetherwith these valves, as previously discussed) may be closed to prevent anyfluid transfer from occurring from the dialysate side to the blood side.During the time the blood flow pump is not delivering, the insidedialysate pumps are effectively frozen, and the inside dialysate pumpdelivery stroke resumes once the blood flow pump starts deliveringagain. The inside dialysate pump fill pressure can be set to a minimalpositive value to ensure that the pump operates above atmosphere atminimal impedance. Also, the inside dialysate pump delivery pressure canbe set to the blood flow pump pressure to generally match pressures oneither side of the dialyzer, minimizing flow across the dialyzer duringdelivery strokes of the inside dialysate pump.

In another embodiment, the inside dialysate pump delivers dialysate tothe dialyzer at a pressure slightly above the pressure at which blood isdelivered to the dialyzer. This ensures that a full balance chamber ofclean dialysate gets delivered to the dialyzer. On the return side, theinside dialysate pump can fill with spent dialysate from the dialyzer ata slightly lower pressure than the outlet pressure on the blood side ofthe dialyzer, ensuring that the receiving dialysate pump chamber canfill. This in turn ensures that there is enough dialysate available tocomplete a full stroke in the balancing chamber. Flows across thesemi-permeable membrane caused by these differential pressures will tendto cancel each other; and the pumping algorithm otherwise attempts tomatch the average pressures on the dialysate and blood sides of thedialyzer.

It is generally beneficial to keep the blood flow as continuous aspossible during therapy, as stagnant blood flow can result in bloodclots. In addition, when the delivery flow rate on the blood flow pumpis discontinuous, the balancing pump may pause its stroke morefrequently, which can result in discontinuous and/or low dialysate flowrates. However, the flow through the blood flow pump can bediscontinuous for various reasons. For instance, pressure may be limitedwithin the blood flow pump, e.g., to +600 mmHg and/or −350 mmHg toprovide safe pumping pressures for the patient. For instance, duringdual needle flow, the two pod pumps of the blood flow pump can beprogrammed to run 180° out of phase with one another. If there were nolimits on pressure, this phasing could always be achieved. However toprovide safe blood flow for the patient these pressures are limited. Ifthe impedance is high on the fill stroke (due to a small needle, veryviscous blood, poor patient access, etc.), the negative pressure limitmay be reached and the fill flow rate will be slower then the desiredfill flow rate. Thus the delivery stroke must wait for the previous fillstroke to finish, resulting in a pause in the delivery flow rate of theblood flow pump. Similarly, during single needle flow, the blood flowpump may be run at 0° phase, where the two blood flow pump pod pumps aresimultaneously emptied and filled. When both pod pumps are filled, thevolumes of the two pod pumps are delivered. In an embodiment, thesequence of activation causes a first pod pump and then a second podpump to fill, followed by the first pod pump emptying and then thesecond pod pump emptying. Thus the flow in single needle or single lumenarrangement may be discontinuous.

One method to control the pressure saturation limits would be to limitthe desired flow rate to the slowest of the fill and deliver strokes.Although this would result in slower blood delivery flow rates, the flowrate would still be known and would be more continuous, which wouldallow for more accurate and continuous dialysate flow rates. Anothermethod to make the blood flow rate more continuous in single needleoperation would be to use maximum pressures to fill the pods so the filltime would be minimized. The desired deliver time could then be set tobe the total desired stroke time minus the time that the fill stroketook. However, the less continuous the blood flow, the more thedialysate flow rate may have to be adjusted upward during blood deliveryto the dialyzer to make up for the time that the dialysate pump isstopped when the blood flow pump is filling. If this is done with thecorrect timing, an average dialysate flow rate taken over severalstrokes can still match the desired dialysate flow rate.

FIG. 5 shows a close up of the directing circuit 142 in the FIG. 2embodiment. In this embodiment, the directing circuit 142 can providedialysate from a dialysate tank 169 via a dialysate pump 159 to a heater72 and the ultrafilter 73. The heater 72 may be used to warm thedialysate to body temperature, and/or a temperature such that the bloodin the blood flow circuit is heated by the dialysate, and the bloodreturning to the patient is at body temperature or higher. In somecases, the heater 72 may be connected to a control system such thatdialysate that is incorrectly heated (i.e., the dialysate is too hot ortoo cold) may be recycled (e.g., back to the dialysate tank 169) or sentto drain instead of being passed to the dialyzer. The heater 72 may alsobe used, in some embodiments, for disinfection or sterilizationpurposes. For instance, water may be passed through the hemodialysissystem and heated using the heater such that the water is heated to atemperature able to cause disinfection or sterilization to occur, e.g.,temperatures of at least about 70° C., at least about 80° C., at leastabout 90° C., at least about 100° C., at least about 110° C., etc.

The flow of dialysate through the directing circuit 142 may becontrolled (at least in part) by operation of the dialysate pump 159. Inaddition, the dialysate pump 159 may control flow through the balancingcircuit 143. For instance, as discussed above, fresh dialysate from thedirecting circuit 142 flows into balancing chambers 341 and 342 ofbalancing circuit 143. The dialysate pump 159 may be used as a drivingforce to cause the fresh dialysate to flow into these balancingchambers. In one set of embodiments, dialysate pump 159 includes a podpump, e.g., similar to those described above.

The dialysate may also be filtered to remove contaminants, infectiousorganisms, pathogens, pyrogens, debris, and the like, for instance,using an ultrafilter 73. The ultrafilter 73 may be positioned in anysuitable location in the dialysate flow path, for instance, between thedirecting circuit and the balancing circuit, e.g., as shown, and/or theultrafilter 73 may be incorporated into the directing circuit or thebalancing circuit. If an ultrafilter is used, its pore size may bechosen to prevent species such as these from passing through the filter.

In some cases, the ultrafilter 73 may be operated such that waste fromthe filter (e.g., the retentate stream) is passed to a waste stream,such as waste line 39 in FIG. 5. In some cases, the amount of dialysateflowing into the retentate stream may be controlled. For instance, ifthe retentate is too cold (i.e., heater 72 is not working, or heater 72is not heating the dialysate to a sufficient temperature, the entiredialysate stream (or at least a portion of the dialysate) may bediverted to waste line 39, and optionally, recycled to dialysate tank169 using line 48. Flow from the filter 73 may also be monitored forseveral reasons, e.g., using temperature sensors (e.g., sensors 251 and252), conductivity sensors (for confirming dialysate concentration,e.g., sensor 253), or the like. An example of such sensors is discussedbelow; further non-limiting examples can be seen in a U.S. patentapplication Ser. No. 12/038,474, filed Feb. 27, 2008.

The ultrafilter and the dialyzer may provide redundant screening methodsfor the removal of contaminants, infectious organisms, pathogens,pyrogens, debris, and the like. Accordingly, any contaminant would haveto pass through both the ultrafilter and the dialyzer before reaching apatient's blood. Even in the event that either the ultrafilter ordialyzer integrity fails, the other may still be able to maintaindialysate sterility and prevent contaminants from reaching the patient'sblood.

The directing circuit 142 may also be able to route used dialysatecoming from a balancing circuit to a drain, e.g., through waste line 39to drain 31. The drain may be, for example, a municipal drain or aseparate container for containing the waste (e.g., used dialysate) to beproperly disposed of. In some cases, one or more check or “one-way”valves (e.g., check valves 215 and 216) may be used to control flow ofwaste from the directing circuit 142 and from the system 5. Also, incertain instances, a blood leak sensor (e.g., sensor 258) may be used todetermine if blood is leaking through the dialyzer 14 into the dialysateflow path. In addition, a liquid sensor can be positioned in acollection pan at the bottom of the hemodialysis unit to indicateleakage of either blood or dialysate, or both, from any of the fluidcircuits.

The directing circuit 142 may receive water from a water supply 30,e.g., from a container of water such as a bag, and/or from a device ableto produce water, e.g., a reverse osmosis device. In some cases, thewater entering the system is set at a certain purity, e.g., having ionconcentrations below certain values. The water entering into thedirecting circuit 142 may be passed on to various locations, e.g., to amixing circuit 25 for producing fresh dialysate and/or to waste line 39.In some cases, valves to the drain 31 and various recycle lines areopened, and conduits 67 may be connected between directing circuit 142and blood flow circuit 141, such that water is able to flow continuouslyaround the system. If heater 72 is also activated, the water passingthrough the system will be continuously heated, e.g., to a temperaturesufficient to disinfect the system.

FIG. 6 shows a close-up view of the mixing circuit 25 in theillustrative embodiment of FIG. 2. Water from the directing circuit 142flows into the mixing circuit 25 due to action of a pump 180. In thisembodiment, the pump 180 includes one or more pod pumps, similar tothose described above. In some cases, a portion of the water is directedto reagent ingredients 49, e.g., for use in transporting theingredients, such as the bicarbonate 28, through the mixing circuit 25.In some cases, sodium chloride and/or the sodium bicarbonate 28 may beprovided in a powdered or granular form, which is mixed with waterprovided by the pump 180. Bicarbonate from bicarbonate source 28 isdelivered via bicarbonate pump 183 to a mixing line 186, which alsoreceives water from the directing circuit 142. Acid from an acid source29 (which may be in a liquid form) is also pumped via an acid pump 184to the mixing line 186. The ingredients 49 (water, bicarbonate, acid,NaCl, etc.) are mixed in mixing chamber 189 to produce dialysate, whichthen flows out of mixing circuit 25 to the directing circuit 142.Conductivity sensors 178 and 179 are positioned along mixing line 186 toensure that as each ingredient is added to the mixing line, it is addedat proper concentrations. The volumes delivered by the water pump 180and/or the other pumps may be directly related to the conductivitymeasurements, so the volumetric measurements may be used as across-check on the composition of the dialysate that is produced. Thismay ensure that the dialysate composition remains safe even if aconductivity measurement becomes inaccurate during a therapy.

FIG. 7 shows a perspective view of a hemodialysis system 5 thatincorporates various aspects of the invention. In accordance with oneaspect of the invention, the system 5 includes a dialysis unit 51 and apower unit module 52 that are shown joined together. In this embodiment,the dialysis unit 51 has a housing that contains suitable components forperforming hemodialysis, such as a dialyzer, one or more pumps tocirculate blood through the dialyzer, a source of dialysate, and one ormore pumps to circulate the dialysate through the dialyzer. For example,the dialysis unit 51 may include the mixing circuit 25, blood flowcircuit 141, the balancing circuit 143 and the directing circuit 142 asdescribed above. The dialysis unit 51 may also include all blood circuitconnections and dialysate fluidic connections needed for operation ofthe system 5. Patient access and other connections may be revealed byopening side-by-side vertical doors 53 via a handle 54 at a front sideof the dialysis unit 51 housing. In this embodiment, the dialysis unit51 includes a control interface 55 (attached to the housing by aflexible cable in this embodiment) that a user may use to controloperation of the dialysis unit 51. The control interface 55 may includea display screen with a touch sensitive overlay to allow touch controland interaction with a graphical user interface presented on the screen.The control interface 55 may also include other features, such as pushbuttons, a speaker, a microphone for receiving voice commands, a digitalcamera, and so on. The back side of the control interface 55 may includea retractable “kick-stand” (not shown) that allows the control interface55 to be positioned on top of the dialysis unit 51 housing. Deployingthe retractable “kick-stand” permits the control interface 55 to beplaced in a near-vertical position to allow proper viewing of thedisplay screen. In other embodiments, control interface 55 may comprisea tablet-style computer or hand-held electronic communications device,either of which may communicate wirelessly with a controller housedwithin dialysis unit 51. Examples of wireless communications means mayinclude Bluetooth® technology or wireless local area network technologysuch as Wi-Fi®.

The power unit 52 housing may contain suitable components for providingoperating power to the dialysis unit 51, e.g., pneumatic pressure/vacuumto power the pumps, valves and other components of the dialysis unit 51.“Pneumatic,” as used herein, means using air or other gas to move aflexible diaphragm or other member. (It should be noted that air is usedby way of example only, and in other embodiments, other control fluids,such as nitrogen (N₂), CO₂, water, an oil, etc., may be used). Asdiscussed above, the pumps and valves of the dialysis unit 51 mayoperate on pneumatic power, and thus the power unit 52 may provide oneor more pneumatic sources for use by the dialysis unit 51. In this way,the dialysis unit 51 need not necessarily be arranged to generate and/orstore the necessary pneumatic power needed, but instead may rely on thepower unit module 52. The power unit 52 may include one or morepneumatic pumps to generate desired air pressure and/or vacuum, one ormore accumulators or other devices to store pneumatic power, valves,conduits and/or other devices to control flow of pneumatic power in thepower unit 52, as well as a controller having suitable components, suchas a programmed general purpose data processor, memory, sensors (e.g.,to detect pressure, temperature, etc.), relays, actuators, and so on.

In one embodiment, the pneumatic power (e.g., air under suitablepressure/vacuum) may be supplied by the power unit 52 to the dialysisunit 51 via one or more supply tanks or other pressure sources. Forinstance, if two tanks are used in the power unit 52, one supply tankmay be a positive pressure reservoir, and in one embodiment, has a setpoint of 750 mmHg (gauge pressure) (1 mmHg is about 133.3 pascals). Theother supply tank can be a vacuum or negative pressure reservoir, and inone embodiment, has a set point of −450 mmHg (gauge pressure). Thispressure difference may be used, for instance, between the supply tanksand the required pod pump pressure to allow for accurate control of thevariable valves to the pod pumps. The supply pressure limits can be setbased on maximum pressures that can be set for the patient blood flowpump plus some margin to provide enough of a pressure difference forcontrol of the variable valves. Thus, in some cases, the two tanks maybe used to supply pressures and control fluids for all of the dialysisunit 51 functions.

In one embodiment, the power unit 52 may include two independentcompressors to service the supply tanks. Pressure in the tanks can becontrolled using any suitable technique, for instance, with a simple“bang-bang” controller (a controller that exists in two states, i.e., inan on or open state, and an off or closed state), or with moresophisticated control mechanisms, depending on the embodiment. As anexample of a bang-bang controller, for the positive tank, if the actualpressure is less than a set point, the compressor servicing the positivetank is turned on. If the actual pressure is greater than a set point,the compressor servicing the positive tank is turned off. The same logicmay be applied to the vacuum tank and control of the vacuum compressorwith the exception that the sign of the set point term is reversed. Ifthe pressure tanks are not being regulated, the compressor is turned offand the valves are closed.

Tighter control of the pressure tanks can be achieved by reducing thesize of the hysteresis band, however this may result in higher cyclingfrequencies of the compressor. If very tight control of these reservoirsis required, the bang-bang controller could be replaced with aproportional-integral-derivative (“PID”) controller and using pulsewidth modulation (“PWM”) signals on the compressors. Other methods ofcontrol are also possible.

Other pressure sources may be used in other embodiments, and in somecases, more than one positive pressure source and/or more than onenegative pressure source may be used. For instance, more than onepositive pressure source may be used that provides different positivepressures (e.g., 1000 mmHg and 700 mmHg), which may be used to minimizeleakage. For example, high positive pressure can be used to controlvalves, whereas lower positive pressures can be used to control pumps.This limits the amount of pressure that can potentially be sent to thedialyzer or to the patient, and helps to keep actuation of the pumpsfrom overcoming the pressures applied to adjacent valves. A non-limitingexample of a negative pressure is −400 mmHg. In some cases, the negativepressure source may be a vacuum pump, while the positive pressure pumpmay be an air compressor.

In an embodiment, power unit 52 comprises a housing that may containcomponents as shown in FIG. 7 a. In this example, a pump and pneumaticstorage assembly is arranged to fit within power unit 52, and comprisesa positive pressure pump 60, a negative pressure or vacuum pump 61, ahigh-positive pressure reservoir 62, a lower-positive pressure reservoir63, a negative pressure reservoir 64, and a dehumidification or‘chiller’ unit 65. The high-positive pressure reservoir 62, for example,may store air at pressures of about 1000-1100 or more mmHg, and thelower-positive pressure reservoir 63, for example, may store air atpressures of about 700-850 mmHg. The pressurized air generated bypositive pressure pump 60 may be used to fill reservoir 63 byinterposing a pressure regulator (not shown) between the outlet of pump60 and the inlet of reservoir 63.

Chiller 65, or another suitable dehumidifier, may be interposed betweenthe outlet of positive pressure pump 60 and the inlet of the one or morepositive pressure reservoirs 62 and/or 63. De-humidification of thepressurized air may prevent water condensation inside pneumatic lines ormanifold passages and valves driven by the positive pressure reservoirs62 and/or 63. As shown schematically in FIG. 7 b, the chiller 65 mayinclude a metal coil conduit 66 through which air from compressor 60 ispassed, and in which water may be condensed from the compressed air. Acooling element 67 may separate the compressed air coils from a heatexchanger 68, through which ambient air may be drawn, warmed andexhausted by fan 69. The heat exchanger rejects heat to the ambientenvironment, and a water trap 70 separates the condensed water from thecompressed air. The dried compressed air is then available for storagein reservoir 62 (or via a pressure regulator for storage in low pressurereservoir 63), or for delivery to downstream devices 71 such as a valvedpneumatic manifold. Cooling element 67 may be a commercially availableelectrically powered Peltier device such as device model C1-34-1604 fromTellurex, Inc. FIG. 7c shows an example of how chiller 65 may bearranged and configured to fit within the confines of power unit 52.

Moreover, the power unit 52 may be selectively connectable to thedialysis unit 51, e.g., to allow different power units 52 to beinterchanged. For example, the dialysis unit 51 may be arranged to workwith different types of power units 52, such as power units 52 that useelectrical power to generate the pneumatic power supply, as well aspower units 52 that use stored pneumatic power (e.g., pressurized airstored in one or more high pressure tanks). Thus, a power unit 52 may beinterchanged for another unit 52, in case of failure or otherrequirements. For example, it may be desired to use the system 5 in anarea where noise generation is unacceptable, such as when nearby peopleare sleeping. In this case, it may be desirable to use a power unit 52that uses stored pneumatic power, rather than a unit 52 that generatespneumatic power by running pumps or other noise generating equipment. Asshown in FIG. 8, the power unit 52 may be disconnected from the dialysisunit 51 by manipulating a handle 521. For example, turning the handle521 may unlock the power unit 52 from the dialysis unit 51, disengagingnot only mechanical connections between the housings, but also powerand/or communications connections between the two. An interface (notshown) between the dialysis unit 51 and the power unit 52 may permit theunits to exchange pneumatic power (from the power unit 52 to thedialysis unit 51) as well as electrical power, control communications,and other. The dialysis unit 51 may have connection points forelectrical power (e.g., standard 115V, 15 amp power found in most homepower outlets), external communication (such as Ethernet, or any othersuitable connection suitable for communication), a water supply, and soon. The dialysis unit 51 may provide electrical power or otherconnections to the power unit 52, if desired.

The dialysis unit 51 may include a controller to control flow of controlfluid for various components of the system 5, as well as perform otherdesired functions. In some cases, the control fluid may be held atdifferent pressures within the various tubes or conduits. For instance,some of the control fluid may be held at positive pressure (i.e.,greater than atmospheric pressure), while some of the control fluid maybe held at negative pressures (less than atmospheric pressure). Inaddition, in certain embodiments, the controller may have componentsthat are kept separate from the various liquid circuits. Thisconfiguration has a number of advantages. For example, in oneembodiment, the liquid circuits in the dialysis unit 51 may be heated todisinfection temperatures and/or exposed to relatively high temperaturesor other harsh conditions (e.g., radiation) to effect disinfection,while electronic components of the controller may not be exposed to suchharsh conditions, and may even be kept separate by an insulating wall(e.g., a “firewall”) or the like. That is, the dialysis unit housing mayhave two or more compartments, e.g., one compartment with electronic andother components that may be sensitive to heat or other conditions, andanother compartment with liquid circuit components that are heated orotherwise treated for disinfection.

Thus, in some embodiments, the system 5 may include a “cold” section(which is not heated), and a “hot” section, portions of which may beheated, e.g., for disinfection purposes. The cold section may beinsulated from the hot section through insulation. In one embodiment,the insulation may be molded foam insulation, but in other embodimentscan be any type of insulation, including but not limited to a sprayinsulation, an air space, insulation cut from sheets, etc. In oneembodiment, the cold section includes a circulation system, e.g., a fanand/or a grid to allow air to flow in and out of the cold box. In somecases, the insulation may be extended to cover access points to the“hot” section, e.g., doors, ports, gaskets, and the like. For instance,when the “hot” section is sealed, the insulation may completely surroundthe “hot” section in some cases.

Non-limiting examples of components that may be present within the“cold” section include power supplies, electronics, power cables,pneumatic controls, or the like. In some cases, at least some of thefluids going to and from the “hot” section may pass through the “cold”section; however, in other cases, the fluids may pass to the “hot”section without passing through the “cold” section.

Non-limiting examples of components that may be present within the “hot”section include cassettes (if present), fluid lines, temperature andconductivity sensors, blood leak sensors, heaters, other sensors,switches, emergency lights, or the like. In some cases, some electricalcomponents may also be included in the “hot” section. These include, butare not limited to, a heater. In one embodiment, the heater can be usedto heat the hot box itself, in addition to fluid. In some embodiments,the heater 72 heats the entire “hot” section to reach a desiredtemperature.

In accordance with an aspect of the invention, the dialysis unit 51housing may include vertical side-by-side doors that can be opened toexpose all mechanical interface points for blood flow circuitry andconnections for dialysate circuitry, i.e., all connection points forpatient blood connections and acid/bicarbonate connections, that must bemade by a user to use the dialysis unit 51. FIG. 9 shows a front view ofthe dialysis unit 51 with the vertical side-by-side doors 53 in a closedstate. In this arrangement, the doors 53 may block access to connectionpoints for patient blood connections and acid/bicarbonate connections aswell as seal the interior of the unit housing so as to allow heatretention suitable for disinfection. The seal provided by the doors 53may be hermetic, preventing or substantially resisting any air exchangebetween the housing interior and an exterior environment, or may be of asomewhat lesser quality yet still allow for disinfection.

In this embodiment, the doors 53 are connected to the dialysis unit 51housing by a dual hinge arrangement such that the doors 53 can be openedto two different states of opening. FIGS. 10-13 show the doors 53 in afirst state of opening. In this state, the doors 53 expose all user-madeconnections for the blood circuit connections and for the dialyzercircuitry, including the dialyzer 14 itself and for reagent materials,such as consumable acid/bicarbonate materials. This position alsoexposes several other features, such as holders 531 for anacid/bicarbonate container (not shown) and hooks 532 that may be used tohold any suitable item, such as the control interface 55, which may behung by its handle on one of the hooks 532. (See also FIG. 7 which showsa hook 532 on the front of the left door 53 which may be folded out toreceive the control interface 55 or other item.) The holders 531 in thisembodiment may be folded down from their position shown in the figures(i.e., folded up and into recesses in the doors 53) so as to extendhorizontally from the doors 53. The holders 531 have a “C” shapedreceiving section to receive and hold an acid/bicarbonate container, butof course could be shaped or otherwise arranged in any suitable way.

FIGS. 14-16 show the doors 53 in a second state of opening in which ahinge plate 533 for each door 53 is pivoted outward and away from thedialysis unit housing 51. The hinge plates 533, which in this embodimentextend vertically along almost the entire height of the dialysis unithousing 51, are pivotally attached to the doors 53 at a first, outerend, and are pivotally attached at a second inner end to the dialysisunit housing 51. (Of course, it should be understood that the hingeplates 533 could be arranged and/or positioned differently, e.g., at thetop and bottom of the doors 53 as is found in many refrigerator doorarrangements, each plates 533 may include two or more portions that arevertically separated from each other, etc.) Magnets 534 attached to thehinge plates 533 may interact with corresponding magnets (or othersuitable components, such as a steel elements) attached to the dialysisunit housing 51 so as to attract the hinge plates 533 toward thedialysis unit housing 51, thus tending to keep the hinge plates 533 inthe position shown in FIGS. 10-13. (Of course, the magnets 534 could bepositioned on the unit housing, and the hinge plates 533 could havesuitable elements (such as pieces of steel) that are attracted to themagnets 534.) The doors 53 in this embodiment also include magnetsattached near the hinge plates 533 so that when the doors 53 are openedto the first state as shown in FIGS. 10-13, the magnets interact withcorresponding magnets in the hinge plates 533 to help keep the doors 53in an open position relative to the hinge plate 533. These magnets willalso help maintain the relative position of the doors 53 and the hingeplates 533 when the hinge plates 533 are opened to the second stateshown in FIGS. 13-16.

Although magnets are used in this illustrative embodiment as part of aretainer member to help the doors 53 and/or hinge plates 533 stay in aparticular state of opening or closing, other arrangements for aretainer member are possible. For example, the hinge connection betweenthe doors 53 and the hinge plates 533 and/or the connection between thehinge plates 533 and the housing 51 may include a detent arrangementthat serves to resiliently hold the door 53 or hinge plate 533 in aparticular position relative to the other part (the hinge plate orhousing, respectively). In another embodiment, one or more springs maybe used to help maintain the doors 53 in an open position relative tothe hinge plates 533. In yet another embodiment, the hinge plates 533may have a friction or interference fit with a portion of the housing 51that tends to maintain the hinge plates 533 in the closed position(adjacent the housing). Accordingly, a retainer member that functions tohelp maintain a door 53 in a particular position relative to its hingeplate 533, and/or that functions to help maintain a hinge plate 533 in aparticular position relative to the housing 51, may take any one of anumber of possible arrangements.

In accordance with another aspect of the invention, opening of the doorsto the dialysis unit housing may reveal all of the user-made connectionsfor blood circuit connections and dialysate fluidic connections neededfor operation of the system 5. For example, as shown in FIG. 17, withthe doors 53 in an open position (either the first or second state ofopening) a front panel 511 of the dialysis unit 51 may be exposed. Inthis embodiment, the front panel 511 carries several items or connectionpoints that must be accessed by a user. For example, the dialyzer 14,which must be periodically replaced, is mounted to the front panel 511.The dialyzer 14 must be connected not only to the blood flow circuit141, but also the balancing circuit 143. Also, a connection point 512for an acid/bicarbonate source 49 is located at a lower end of the frontpanel 511. It is at this connection point 512 that a user may connect asource of consumable reagent ingredients 49 used by the dialysis unit 51in making dialysate. An occluder 513 is also mounted on the front panel511. The occluder 513 receives tubes of the blood flow circuit andcontrols the open/closed state of the tubes based on system operation.The function of the occluder 513 is discussed in more detail in U.S.application Ser. No. 12/198,947, filed Aug. 27, 2008 (under AttorneyDocket Number D0570.70020US00 (G28)) and below. In short, the occluder513 allows flow through the arterial and venous lines of the blood flowcircuit unless there is a system problem, such as a leak, pump failure,overpressure situation, etc. In such case, the occluder 513automatically closes the blood lines to prevent all flow to or from thepatient. Also exposed on the front panel 511 are blood line connectionpoints 514 for connecting the arterial and venous blood lines 203, 204of the blood flow circuit 141 with the directing circuit 142 (asexplained above with reference to FIGS. 2 and 3, the blood flow circuit141 may be connected to the directing circuit 142). This connection isnormally made at the end of treatment to allow the system to clean anddisinfect the blood flow circuit 141. The front panel 511 also has a setof control ports 515 that mate with corresponding control ports on theblood pump portion of the blood flow circuit 141. The control ports 515provide controlled levels of air pressure and/or vacuum to control theopen/closed state of valves and to power the pumps of the blood flowcircuit 141.

In another aspect of the invention, FIG. 17a shows a perspective view ofa control port assembly 615 onto which a blood pump assembly 13 may bemounted, and with which the fluidic control ports of the blood pumpassembly 13 can connect. Shown, for example, are control ports 616 forcontrolling the actuation of valves on a blood pump assembly 13, andcontrol ports 617 for controlling the actuation of pumps on a blood pumpassembly 13. In order to secure a blood pump assembly 13 onto controlport assembly 615, a latch member or other engagement device may beprovided at one or more sides of, or within, control port assembly 615,or at a portion of front panel assembly 511 adjacent to, or within, thelocation of the control port assembly 615. (In the example shown,control port assembly 615 may be reversibly mounted onto front panelassembly 511 via retaining tabs 619). Alternately, or in addition, adisengagement or other ejection feature for a blood circuit assembly maybe provided to help with removal of a blood pump assembly or other partsof a blood circuit assembly from the front panel 511. For example, apair of cassette latching and ejection assemblies may be mounted onopposite sides of the control port assembly 615. In the FIG. 17aembodiment, a blood circuit assembly engagement device includes latch orretainer members 618 a and 618 b pivotably mounted to the sides ofcontrol port assembly 615. Preferably, the pivotal connections (e.g.,pivotal connection 620) of latch members 618 a and 618 b are biased by asuitably disposed spring to urge latch members 618 a and 618 b to rotatetoward each other and toward the surface of control port assembly 615,so that they can maintain contact with the edges or other parts of ablood pump assembly 13 (shown in cross-section in FIG. 17b ) mounted onthe control port assembly 615. This is more clearly shown in FIG. 17 b,which is a top, sectional view of control port assembly 615, onto whichis mounted a blood pump assembly 13. Latch member 618 b is shown in FIG.17b in its normally biased position, securing the outer edge of bloodpump assembly 13 in connection with control port assembly 615. Latchmember 618 a, on the other hand, is shown in a partially retractedposition, allowing blood pump assembly 13 to be partially separated fromcontrol port assembly 615. In a fully retracted position (not shown),latch member 618 a or 618 b clears the front edge of blood pump assembly13, allowing it either to be removed from or installed or mounted ontocontrol port assembly 615.

As shown in FIGS. 17a and 17 b, in addition to a latch or retainermember 618 a and 618 b that may help to hold blood pump assembly 13 ontocontrol port assembly 615, a separation assist member (or ejectorelement or member) 622 a or 622 b may also be included to assist a userin separating blood pump assembly 13 from control port assembly 615, andlifting it away from control port assembly 615. The separation assistmember 622 a or 622 b may be pivotably mounted on the front panelassembly 511 in a location suitable for a contacting portion 624 a or624 b of the separation assist member 622 a and 622 b to contact an edgeof the undersurface 113 a of blood pump assembly 13 to help lift it offthe control port assembly 615 when the separation assist member 622 a or622 b is rotated in an outward fashion. The engagement device mayinclude an actuator to actuate the retainer members 618 and/or theejector elements 622, such as a thumb- or finger-contacting element 626a or 626 b that can be pressed laterally by a user to pivot separationassist member 622 a or 622 b outward to engage contacting portion 624 aor 624 b with the undersurface 113 a of blood pump assembly 13.Preferably, a spring 628 may be included near the pivotal connection ofseparation assist member 622 a or 622 b, and suitably disposed to biasseparation assist member 622 a or 622 b to urge contacting portion 624 aor 624 b away from contact with the undersurface 113 a of blood pumpassembly 13. That way, no intrinsic force from separation assist member622 a or 622 b is acting to push blood pump assembly 13 away fromcontrol port assembly 615. In another preferred embodiment, separationassist member 622 a or 622 b may be pivotably mounted to latch member618 a or 618b, as shown in FIG. 17 a. In this embodiment, a user mayengage separation assist member 622 a or 622 b with the undersurface 113a of blood pump assembly 13, and simultaneously disengage latch member618 a and 618 b from contact with the front edge or surface of bloodpump assembly 13 by means of a single outward push of thumb- orfinger-contacting element 626 a or 626 b. Thus, with the outward push ofone or more actuators, such as a single element 626 a or 626 b, bloodpump assembly 13 may be alternately seated and secured onto control portassembly 615, or separated from control port assembly 615, facilitatingthe installation and/or removal of blood pump assembly 13.

FIG. 17C shows another embodiment of a blood circuit assembly engagementdevice, that in this embodiment includes a pair of blood pump cassetteretainer and ejector elements. In this embodiment, cassette retainerelement 630 includes a contacting member 632 that makes contact with anejector (or separation assist) element 634. In a retracted state,ejector element 634 is positioned in a recessed area 636 of the bloodpump pod recess 638 in the control port assembly 640. As retainerelements 630 are pivoted outward (direction of arrows in FIG. 17C),contacting member 632 presses against a proximal end 642 of the ejectorelement 634, whereupon ejector element 634 rotates about pivot axis 644,causing a distal end 646 of ejector element 634 to lift out of recess636 to engage the rigid back wall of the actuation chamber of a mountedpump cassette, which is positioned within the blood pump pod recess 638.FIGS. 17D and 17E show isolated views of the engagement device, with aejector element 634 in retracted (FIG. 17D) and extended (FIG. 17E)positions. In FIG. 17D, retainer element 630 is in a retaining position,with retention elements 648 rotated inward toward the center of controlport assembly 640, and ejector element 634 in a recessed position withproximal portion 642 elevated and distal portion 646 depressed. In FIG.17E, retainer element 630 is in a release position, with retentionelements 648 rotated outward away from the center of control portassembly 640, and ejector element 634 in a raised position with proximalportion 642 lowered by contacting member 632 and distal portion 646raised out of recess 636 to eject a cassette mounted in control portassembly 640. Thumb rest (actuator) 650 is shaped to conveniently allowa user to apply an outward force to release a cassette by applying onethumb on each of the opposing latching members 630 in a completeassembly as shown in FIG. 17C. In an embodiment, retainer element 630rotates about an axis formed by pinions 652, equipped with springs 654biased in a latching or retaining direction to help keep a cassettesecurely mounted on control port assembly 640. FIG. 17F shows a frontview of a blood pump cassette 1000 (which is part of a blood circuitassembly) mounted to a panel of a dialysis unit, such as an exposedfront panel 511. FIGS. 17G and 17H show cross-sectional views of bloodpump cassette 1000 along the lines 17G-17G and 17H-17H, respectively,with the cassette 1000 properly seated on control port assembly 640.FIG. 17G shows the relationship between contacting members 632, ejectorelements 634, and the rigid back walls 658 of the pump actuationchambers of cassette 1000. Ejector elements 634 are shown to be in fullyretracted positions in their respective recessed areas 636 to allow pumpcassette 1000 to be fully seated. FIG. 17H shows the relationshipbetween retention elements 648 and the front plate 656 of cassette 1000.In this case, retention elements 648 are brought into apposition withthe front plate 656, securing cassette 1000 onto control port assembly640.

FIG. 17I shows a front view of the blood pump cassette from FIG. 17F inthe process of being disengaged from the panel 511 of a dialysis unit.FIGS. 17J and 17K show cross-sectional views of blood pump cassette 1000with the cassette 1000 partially lifted from its engagement with controlport assembly 640. FIG. 17J shows the relationship between contactingmembers 632, ejector elements 634, and the rigid back walls 658 of thepump actuation chambers of cassette 1000. In this case, the distal ends646 of ejector elements 634 are contacting and elevating cassette 1000from its fully seated position in control port assembly 640. FIG. 17Kshows the relationship between retention elements 648 and the frontplate 656 of cassette 1000. In this case, the front plate 656 has beenelevated above the retaining surface of retainer elements 648.

Also exposed on the front panel 511 in FIG. 17 is a user control panel510. The user control panel 510 includes one or more buttons permittingthe user to bypass the graphical user interface on control interface 55,providing an alternate method to control certain functions (e.g.,critical functions) during hemodialysis. This may be important, forexample, if the control interface 55 should ever fail during a dialysistreatment session. Non-limiting examples of critical functions caninclude a “stop dialysis” or “pause dialysis” command and an “infusedialysate solution” command.

FIG. 17 does not show the arterial and venous lines 203, 204 for theblood flow circuit 141 because in this embodiment and in accordance withanother aspect of the invention, the blood flow circuit 141 is formed asa blood circuit assembly that is removable from the front panel 511 ofthe dialysis unit 51, and the blood circuit assembly is not mounted onthe front panel 511 in FIG. 17. FIG. 18 shows a front view of the bloodcircuit assembly 17 in this embodiment along with the dialyzer 14. Theblood circuit assembly 17 includes various components discussed above,for example with reference to FIG. 3, that are mounted to a bloodcircuit organizing tray 171. The arterial and venous lines 203 and 204(e.g., including lengths of flexible silicone tubing) are terminatedwith blood line connectors that, in one aspect of the invention, arearranged to provide a plug-in or press-in connection with the blood lineconnection points 514 as well as provide a screw-type connection usedwith standard patient access points (e.g., luer type patient accessconnectors). The arterial line 203 leads to an inlet at the top of theblood pump 13, which includes two pod pumps 23, valves and othercomponents for controlling blood flow. Associated with the blood pump 13are an air filter 81, an anticoagulant pump 80 (not shown), and ananticoagulant supply 11 (such as a vial of heparin). (Details regardingthe blood pump 13 in this illustrative embodiment may be found in U.S.patent application Ser. No. 11/871,680, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,712, filedOct. 12, 2007, entitled “Pumping Cassette”; U.S. patent application Ser.No. 11/871,787, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,793, filed Oct. 12, 2007, entitled“Pumping Cassette”; and U.S. patent application Ser. No. 11/871,803,filed Oct. 12, 2007, entitled “Cassette System Integrated Apparatus.”)Blood output from the blood pump 13 (the outlet is located at a bottomof the pump 13) flows to an inlet of the dialyzer 14 (at the top of thedialyzer 14), and out of the dialyzer (the dialyzer blood outlet islocated at the bottom of the dialyzer 14) to the inlet of the air trap19. The outlet of the air trap 19 is connected to the venous blood line204. Connections to the inlet and outlet blood ports of the dialyzer 14are made with typical screw-type connections.

FIG. 18a shows a perspective view of a blood pump 13 with an alternativeembodiment of a vial receptacle or vial holder 1206 for holding orcradling a vial of medication 11 (such as, e.g., an anticoagulant) ontoa hollow spike 1208 that is in fluid communication with pump 80(schematically shown in FIG. 3) of the blood pump 13. In thisembodiment, flexible upper arms 1210 serve to hold the body of vial 11in place, and can flex to accommodate vials of various sizes. Lower arms1212 help to align the inverted top of vial 11 with spike 1208 in orderto prevent vial 11 from being spiked at an angle with respect to theinverted top of vial 11. Spiking the top of vial 11 in a substantiallyperpendicular manner may help to avoid any leaking of fluid from withinvial 11 around the outside of spike 1208.

In accordance with another aspect of the invention, the air trap 19 isplaced in the blood flow path after the blood exits the dialyzer andbefore it is returned to the patient. In an embodiment, air trap 19 canhave a spherical or spheroid-shape container (i.e., a container havingan approximately spherical inner wall), and have its inlet port locatednear the top and offset from the vertical axis of the container, and anoutlet at a bottom of the container. (The vertical axis of the containeris arranged in a vertical direction passing through the top and bottom“poles” of the approximately spherical container.) With the inlet portoffset from the vertical axis (in this case set back toward the tray171), blood is introduced into the container in a direction that isapproximately perpendicular to the vertical axis of the container andthat is approximately tangential to the spherical inner wall of thecontainer. The curved shape of the inside wall of the trap can thusdirect the blood to circulate along the inside wall as the bloodgravitates to the bottom of the container (e.g., in a spiral likefashion), facilitating the removal of air bubbles from the blood. Airpresent in the blood exiting the outlet of the dialyzer 14 will enter atthe top of the air trap 19 and remain at the top of the container asblood flows out the outlet at the bottom and to the venous blood line204. By locating the inlet port near the top of trap 19, it is alsopossible to circulate blood through the trap with minimal or no airpresent within the container (as a “run-full” air trap. The ability toavoid an air-blood interface for routine circulation of blood in thetrap can be advantageous. Placing the inlet port at or near the top ofthe container also allows most or all of the air present in the trap tobe removed from the trap by reversing the flow of fluid through theblood tubing (i.e. from the bottom to the top of the trap 19, exitingthrough the inlet port of the trap 19).

In an embodiment, a self-sealing port, such as a self-sealing stopperwith a split septum or membrane, or another arrangement, is located atthe top of the trap, allowing the withdrawal of air from the container(e.g., by syringe). The blood-side surface of the self-sealing membranecan be situated nearly flush with the top of the interior of the trap,in order to facilitate cleaning of the self-sealing port duringdisinfection, e.g., by reversing flow through the air trap using adialysate or other cleaning fluid. Also, the inlet, outlet and internalwall of the container and the self-sealing port may be arranged tosubstantially eliminate stagnation regions, i.e., allow for few or noregions where blood can stagnate or clot. The self-sealing port can alsoserve as a blood sampling site, and/or to allow the introduction ofliquids, drugs or other compounds into the blood circuit. A sealedrubber-type stopper can be used if access with a needle is contemplated.Using a self-sealing stopper with split septum permits sampling andfluid delivery using a needleless system.

FIG. 19 shows the organizing tray 171 for the blood circuit assembly 17without the various blood circuit assembly 17 components mounted. Inaccordance with one aspect of the invention, the organizing tray 171includes handles 172 (in this embodiment, finger pulls) that a user cangrip when mounting/dismounting the blood circuit assembly 17 to thefront panel 511. Inward of the handles 172 are openings 173 that allowspring tabs on the front panel 511 to pass through and engage with theorganizing tray 171 and/or the blood pump 13 cassette to hold the bloodcircuit assembly 17 in place on the front panel 511. In accordance withanother aspect of the invention, the organizing tray 171 includes bloodline engagement members 174 that each have a C-shaped recess or otherhole through which a corresponding blood line 203, 204 passes. (In thiscontext, a “hole” includes a recess like that shown in FIG. 19, athroughbore that has a continuous wall, e.g., as may be made by a drill,or other suitable opening.) As described in more detail below, the bloodline engagement members 174 are used when mounting the blood lines 203,204 in the occluder 513. In short, when mounting the blood lines 203,204 in the occluder 513, the blood lines 203, 204 must be pulled andstretched downwardly (so as to reduce the outside diameter of the line)while being pushed horizontally into slots for the occluder 513. Theblood line engagement members 174 function to both resist downwardpulling on the blood lines 203, 204 (e.g., each line 203, 204 mayinclude a stop ring above the respective engagement member 174 thatcannot be pulled through the recess in the engagement member 174) aswell as permit the user to press inwardly on the engagement member 174to seat the lines 203, 204 in the occluder slots. The engagement members174 are formed integrally with the organizing tray 171 so that a “livinghinge” or relatively flexible portion of the organizing tray ispositioned between the engagement member 174 and the main body of theorganizing tray 171. This arrangement allows the engagement members 174to be pushed inwardly relative to the organizing tray 171 as theconnection portion between the engagement members 174 and the organizingtray main body flexes.

FIG. 20 shows a rear view of the blood circuit assembly 17 with theorganizing tray 171 removed. This view shows the rear side of the bloodpump 13 section with control ports exposed. These control ports matewith corresponding ports 515 on the front panel 511 (see FIG. 17) sothat pneumatic control (e.g., suitable air pressure or vacuum) can beapplied to the pumps and valves to control their operation and flowthrough the blood circuit assembly 17. FIG. 20 also shows the offset ofthe inlet port of the air trap 19, i.e., the inlet port at the top ofthe air trap 19 is arranged to the rear of the vertical axis of thegenerally spherical container portion of the air trap 19.

FIGS. 20A and 20B show exploded, perspective views of an alternativeembodiment of a blood pump cassette 1000. FIG. 20A shows afront-perspective, exploded view of the cassette 1000 having a back(actuation side) plate 1001 that includes a tubing organizer formed withthe back plate on a single molded piece of material. FIG. 20B shows aback-perspective, exploded view of the cassette 1000 of FIG. 20A. Thecassette 1000 shown in FIGS. 20A-20D may be used in place of cassette 13of FIG. 18A and organizing tray 171 of FIG. 19, combining many of thefeatures of these components and substantially reducing the cost andcomplexity of manufacturing and assembling them.

The cassette 1000 includes a back plate 1001 that forms rigid outerwalls of the actuation chambers of various valves and pumps, a mid plate1002 that holds various valve and pump diaphragms and helps to definevarious flow paths in cassette 1000, and a front plate 1003 that formsrigid outer walls of some of the fluid chambers of the various valvesand pumps of cassette 1000. The cassette 1000 optionally furtherincludes a protective cover 1004 that is attachable to the front side ofback plate 1001. The protective cover 1004 may include a holding arm forholding a vial that may be used for later mounting onto vial holder1037. The protective cover 1004 can temporarily hold either an empty orfull vial prior to inserting the vial into a vial holder 1037 for useduring a procedure. That is, a vial may be coupled to a vial holder 1037having a hollow spike that places the vial in vial holder 1037 in fluidcommunication with a fluid port 1038 in the front plate 1003. The vialmay be filled, for example with anticoagulant medication for use duringdialysis, or it may be empty and available for use during cleaning anddisinfection procedures either before or after a dialysis treatment.

The cassette 1000 includes blood flow pumps 1013 and 1014 for movingliquid through the fluid flow side of the cassette 1000. That is, thecassette 1000 includes a left pump 1013 and a right pump 1014 forpumping fluid, which may be blood in the case of a hemodialysisapparatus. The pumps 1013 and 1014 (also referred to herein as podpumps) may be actuated by a control fluid, such as air, a liquid, a gas,or other fluid that enters cassette 1000 through ports on back plate1001. The left pod pump 1013 includes a rigid chamber wall 1005 formedon the front (or top) plate 1003, a rigid chamber wall 1008 formed onthe back (or bottom) plate 1001, a hole 1006 formed on the middle plate1002, and a flexible membrane 1007 that can flex between the rigidchamber walls 1013 and 1008. The space between the rigid chamber wall1013 and the flexible member 1007 defines the fluid or blood side (i.e.,fluid chamber) of the left pump 1013 and the space between the flexiblemembrane 1007 and the rigid chamber wall 1008 defines the pneumatic side(i.e., control chamber) of the left pump 1013. Likewise, the right podpump 1014 includes a rigid chamber wall 1009 formed on the top plate1003, a rigid chamber wall 1012 formed on the bottom plate 1001, a hole1010 formed on the middle plate 1002, and a flexible membrane 1011 thatcan flex between the rigid chamber walls 1009 and 1012. The spacebetween the rigid chamber wall 1009 and the flexible member 1011 definesthe fluid or blood side (i.e., fluid chamber) of the right pump 1009 andthe space between the flexible membrane 1011 and the rigid chamber wall1012 defines the pneumatic side (i.e., control chamber) of the rightpump 1014.

Each of the pod pumps 1013 and 1014 may include a pair of membrane-basedentry/exit valves having fluid flow compartments formed from the topplate 1003 and control compartments formed from the bottom plate 1001.The valves may be actuated by the application of positive or negativefluid (e.g., pneumatic) pressure on individual flexible membranes viacontrol ports on the bottom plate 1001. The fluid valves can be openedand closed to direct fluid flow when the pod pumps are pumping.Depending on how the valve actuations are sequenced in relation to theactuation of their associated pump, fluid may be pumped either in aforward direction, or in a backward direction. Non-limiting examples ofpod pumps are described in U.S. patent application Ser. No. 11/787,212,filed Apr. 13, 2007, entitled “Fluid Pumping Systems, Devices andMethods,” incorporated herein by reference. The pod pumps 1013 and 1014may be operated in any suitable fashion, e.g., synchronously,asynchronously, in-phase, out-of-phase, etc., with fluid flow in eitherdirection.

For hemodialysis applications, in some cases, an anticoagulant (e.g.,heparin, or any other anticoagulant known to those of ordinary skill inthe art) may be mixed with the blood within blood flow cassette 1000.For example, the anticoagulant may be contained within a vial (or otheranticoagulant supply, such as a tube or a bag), and blood flow cassette1000 may be able to receive the anticoagulant vial with a vial holder1037 (which, in one embodiment, includes a needle or hollow spike) thatcan pierce the seal of the vial. The spike may be formed from plastic,stainless steel, or another suitable material, and may be a sterilizablematerial in some cases, e.g., the material may be able to withstandsufficiently high temperatures and/or chemical exposure so as tosterilize the material. As an example, the spike may be used to piercethe seal of the vial, such that anticoagulant can flow into blood flowcassette 1000 to be mixed with the blood in the blood flow path. Inother cases, the vial may be filled or partially filled with water ordialysate during cleaning, disinfecting or priming operations.

A third pump 1015, which can act as a metering pump in some cases, incassette 1000 can be used to control the flow of medication from anattached vial (such as anticoagulant) into a fluid path within thecassette 1000. Metering pump 1015 may be of the same or of a differentdesign from the pumps 1013 and 1014. For example, metering pump 1015 maybe a pod pump and may be actuated by a control fluid, such as air. Forexample, as is shown in FIGS. 20A-20D, the metering pump 1015 mayinclude a rigid chamber wall 1015 formed within the back plate 1001, arigid chamber wall 1018 formed on the mid plate 1002 (see FIG. 20B), anda flexible diaphragm 1015 dividing the pod into a fluid compartment orchamber and a control compartment or chamber. Valves 1028, 1029, 1030may be connected to fluid flow paths joining in various combinationsfluid port 1038, vent port 1019, a fluid flow path leading to or from afirst or second pump (such as pump 1013), and a fluid flow path leadingto or from metering pump 1015. The flow of medication (e.g.,anticoagulant) or other fluid from an attached vial into a main fluidflow path in the cassette 1000 may thus be controlled by metering pump1015; and periodically, air may be introduced from vent port 1019 bymetering pump 1015 into an attached vial through port 1038 to equalizepressure within an attached vial with ambient pressure as medication orother fluid is withdrawn from the vial.

The cassette 1000 may also include an air vent coupled to a port 1019.Air may be introduced into the flow path of metering pump 1015 toequalize pressure in an attached vial with ambient pressure. In thiscase, valve 1029 closes flow between metering pump 1015 and the mainflow path of the first 1013 (or second 1014) pump. In some cases,metering pump 1015 may also introduce air into the main flow path of thefirst 1013 or second 1014 pumps in order to allow a system controller tocontrol the emptying of the blood or liquid carrying components of thesystem.

The pod pumps 1013 and 1014 include raised flow path 1020 and 1021 onthe chambers 1005 and 1009, respectively. The raised flow paths 1020 and1021 allow fluid to continue to flow through the pod pumps 1013 and 1014after the diaphragms (i.e., flexible membranes) 1007 and 1011 reach theend of a stroke.

The cassette 1000 includes several valves 1022, 1023, 1024 and 1025formed within the back plate 1001. The actuation (or pneumatic) side ofthe valves 1022-1025 and 1028-1030 are formed from bottom plate 1001,and have corresponding actuation ports for the entry or egress ofcontrol (e.g. pneumatic) fluid. Several diaphragms 1026 and 1027installed on midplate 1002 complete the valves, while diaphragms 1007,1011 and 1016 complete the pod pumps 1013, 1014 and metering pump 1015.The metering pump 1015 is completed by diaphragm 1016. In a preferredembodiment, the valves are actuated pneumatically, and as the valvediaphragm is pulled away from the adjacent holes in midplate 1002,liquid is drawn in, and as the diaphragm is pushed toward the holes,liquid is pushed through. The fluid flow is directed by the appropriatesequencing of the opening and closing of the valves 1022-1025, and1028-1030.

The metering pump 1015 includes three passageways connected to the fluidchamber 1018 defined in the mid plate 1002. One passageway allows airfrom vent 1019 to be pulled into the metering pump 1015, a secondpassageway allows the air to be pushed to the spike/source containerconnected to vial holder 1037, and also alternately draws liquid fromthe source container or vial, and the third passageway allows the liquidfrom the source container to be pushed by the metering pump 1015 to amain fluid line connected to first pump 1013 (or pump 1014 in analternate embodiment). Valves 1028, 1029, and 1030 determine whether themetering pump 1015 moves fluid or air, and in which direction.

Referring next to FIG. 20C, the inner view of the bottom plate 1100 isshown. The inside view of the pod pumps 1008 and 1012, the metering pump1015, and the valves 1022, 1023, 1028, 1025, 1029, 1030, and 1024actuation/air chambers are shown. The pod pumps 1008 and 1012, themetering pump 1015 and the valves 1022, 1023, 1028, 1025, 1029, 1030,and 1024 are actuated by a pneumatic air source. Referring now to FIG.20D, the outer side of the bottom plate 1100 is shown. The source ofcontrol fluid (e.g. air under positive or negative pressure) isconnected to this side of the cassette. In one embodiment, tubes connectto various ports 1031. In other embodiments, the ports 1031 are arrangedto plug into a control port assembly (e.g., control port assembly 615 inFIG. 17A) on the front panel of dialysis unit 51 (e.g., front panel 511in FIG. 17).

Referring now to FIGS. 20A-20D, the bottom plate 1001 includes variousorganizer features integrated thereon. The bottom plate 1001 includes anair trap retaining member 1032 having tube guides 1033 and 1034 definedon the bottom plate 1001. The tube guides 1033 and 1034 guide a tube toand from an air trap disposed within the air trap retaining member 1032.The bottom plate 1001 also includes additional tube guides 1035 and1039. The bottom plate 1001 also defines a receiving portion 1036 toreceive an electrical connector that may be used in an arrangement tomonitor for disconnection of the arterial or venous lines from a patientduring therapy. FIG. 21 shows a perspective view of the front panel 511of the dialysis unit 51 with the blood circuit assembly 17 mounted tothe front panel 511 without the organizing tray 171. (Normally, theblood circuit assembly 17 would include the organizing tray 171, but thetray 171 is not shown in the example so as to more clearly showcomponents at the front panel 511.) On opposite sides of the blood pump13 cassette, the front panel 511 has spring tabs 516 that extendforwardly and resiliently engage with the blood pump cassette and/or theorganizing tray 171 to retain the blood circuit assembly 17 in place.The tabs 516 may include a barb or other feature to help retain theblood circuit assembly 17 in place. The spring tabs 516 may be flexedoutwardly to release their hold on the blood circuit assembly 17,allowing its removal. However, in the absence of an outwardly directedforce on the spring tabs 516, the tabs 516 will remain engaged with theblood circuit assembly 17. FIG. 22 shows a front view of the front panel511 with the organizing tray 171 of the blood circuit assembly 17included. To remove the blood circuit assembly 17 from the front panel511, a user may place index fingers behind the handles 172 whilesimultaneously placing thumbs on the inner side of the spring tabs 516(the sides nearest the blood pumps 23) and flexing the spring tabs 516outwardly and away from the pumps 23. This causes the spring tabs 516 torelease the blood circuit assembly 17, e.g., disengagement of barbs onthe tabs 516 from the blood pump 13 and/or the organizing tray 171. Ofcourse, to remove the blood circuit assembly 17, other connections mustbe removed, including connections to the dialyzer 14 and the blood lineconnection points 514, as well as removal of the lines 203, 204 from theoccluder 513. When mounting the blood circuit assembly 17 to the frontpanel 511, the organizing tray 171 may be grasped at the handles 172 andproperly aligned, e.g., so that the spring tabs 516 are aligned to passthrough the openings 173 and the control ports of the blood pump 13cassette are aligned with the corresponding ports 515 on the front panel511. The blood circuit assembly 17 may then be simply pushed into place,so that the spring tabs 516 engage with the organizing tray 171 and/orthe blood pump cassette. Other connections can then be made, such asconnections to the dialyzer 14, mounting of the blood lines 203, 204with the occluder 513, etc.

FIG. 21 also shows the slots 517 that hold the blood lines 203, 204 forleading into the occluder 513. The slots 517 define a channel that isslightly smaller than the outside diameter of the blood lines 203, 204so that the lines 203, 204 tend to remain in the slots 517 afterplacement in the slots. This helps to ensure proper association of thelines with the occluder 513. Once the blood circuit assembly 17 ismounted on the spring tabs 516, the user may then engage the blood lines203, 204 with the slots 517 by stretching the lines 203, 204 downward(with the engagement members 174 on the organizing tray 171 engaging thestop ring or other feature on the respective line 203, 204 and resistingthe downward pull) and pushing the lines 203, 204 into a correspondingslot. The lines 203, 204 can be pushed into place by pressing inwardlyon the engagement members 174, which as described above, are flexibleand bend inwardly relative to the organizing tray 171. The lines 203,204 can then be routed through the occluder 513.

In accordance with another aspect of the invention, the front panel 511includes a blood line wrap feature around the periphery of the frontpanel 511. In this illustrative embodiment, the front panel 511 includesflanged portions 518 along the top edge and at lower corners of thefront panel 511. This allows a user to wrap the blood lines 203, 204around the periphery of the front panel 511 by placing the lines 203,204 in a channel defined by the flanged portions 518. The lines 203, 204may be wrapped in a clockwise direction, starting from a point near thebottom of the dialyzer 14, and ending at a point near the lower rightcorner of the front panel 511. The blood lines 203, 204 may then beconnected at the blood line connection points 514, e.g., to allowdisinfecting fluid to be circulated through the blood lines 203, 204. Asa result, the blood lines 203, 204 can be neatly retained on the frontpanel 511, allowing easy access to other components on the front panel511 and allowing the user to close the doors 53 with minimal concern forpinching the blood lines 203, 204 between the doors 53 and the dialyzerunit housing 51. Alternatively, the blood lines 203, 204 may be firstconnected at the blood line connection points 514, and then wrapped in aclockwise direction, starting from a point near the bottom of thedialyzer 14, and ending at a point near the lower right corner of thefront panel 511. This ensures that the blood lines are properlydistributed along the flanged portions 518 to reach the connectionpoints 514. Vertical fences 519 may also be provided along the left andright sides of the front panel 511 to help keep the blood lines 203, 204in a desired position and away from the hinge plates 533 and otherpossible pinch points.

In another aspect, as shown in FIG. 21A, an alternate embodiment of afront panel assembly 811 may include a modular drain assembly (or draincassette) 815 having connection points 814 into which the arterial andvenous blood lines may be connected. As shown in FIG. 5A, the draincassette 815 includes a common pathway to a drain line 31 for both thearterial and venous blood lines during priming, cleaning anddisinfecting operations. Water, dialysate solution or another fluid maybe introduced into the blood pathways of dialysis system 5 through thesemi-permeable membrane of dialyzer 14 in order to expel air from theblood pathways and to prime the blood pathways, or in order to clean anddisinfect the blood pathways. The drain cassette 815 may optionallyinclude a valve in one or both arterial or venous blood pathways. In anembodiment, an electronically controlled valve 831 in or near themodular drain cassette 815 in the venous line may permit the blood pumpson the blood pump cassette 13 to sequentially fill or clear the arterialline while the valve 831 in the venous line is closed, and then fill orclear the venous line upon opening of the valve. In this method, any airor contaminants in the arterial line are forced to the drain outlet ofthe drain cassette 815, rather than into the venous tubing. Alternately,the valve 831 may be arranged to control flow between the arterial lineand the drain, e.g., so contents in the venous line can be forced to thedrain outlet rather than into the arterial line. The drain cassette 815may also optionally include conductivity and/or temperature sensors 834,835. A temperature sensor may be used, for example to monitor thetemperature of the fluid circulating through the blood lines during heatdisinfection. Conductivity sensors may be used to monitor theconductivity of water or dialysate solution being circulated through theblood lines during tests of the urea or sodium clearance of a dialyzer,for example. An electronically controlled drain control valve 207 may beplaced either at the drain outlet of drain cassette 815, or it may bepositioned external to the drain cassette 815 (as shown in FIG. 5A).Drain control valve 207 may be useful, for example, when heated water orchemical disinfectant is being circulated within the blood circuitcomponents of dialysis unit 51. The drain cassette 815 may beconstructed for ease of connection to and disconnection from the frontpanel 511 or 811 of dialysis unit 51. A single handle-operated latch(such as a bayonet connection, for example,) may be included whichsecures the drain cassette 815 onto the front panel by a turn of thehandle.

FIG. 21A also shows an alternate embodiment of a blood pump cassette andorganizing tray assembly. In some embodiments, the organizing tray 822may be incorporated in the pneumatic actuation plate (or back plate) ofthe blood pump cassette 824. FIG. 21B shows the front panel assembly 811with the top and middle plate components of blood pump cassette 824removed for clarity. In this example, the organizing tray 822 and theback plate 816 of blood pump cassette 824 have been combined into asingle molded piece. In this example, the air trap 819 is supported byan extension of the organizing tray 822 and is located in a verticallymore elevated position than in the embodiment shown in FIG. 19 and FIG.29. Moving the air trap to a higher position relative to the occluder813 or the air-in-line detectors 823 may increase the ability of theblood pump in a reverse-flow procedure to draw any air bubbles presentin the venous tubing into the air trap 819. For example, the an inlet ofthe air trap 819 may be supported by the organizing tray 822 at aposition above an outlet of the air trap when the blood circuit assemblyis mounted to a dialysis unit. In addition or alternately, the inletand/or outlet of the air trap may be supported by the organizing tray ata position above a highest point of flexible tubing that extends fromthe outlet of the air trap to the occluder position. Such an arrangementmay help expel any air in the venous tubing into the air trap 819.

In another aspect of the invention, a modular drain cassette may beincluded, having the function of monitoring and draining fluid (such aswater or dialysate solution) flowing through the blood circuit of thedialysis unit 51—the blood circuit including the blood pumps, the bloodflow compartments of the dialyzer, the air trap and the arterial andvenous blood tubing. As shown in FIG. 5A, when the arterial and venousblood tubing is not connected to a patient, it may be connected to adrain chamber/air trap 4703, which ultimately leads to a drain line 31.This connection allows for the circulation of heated water, for example,for cleaning and disinfection of the blood circuit components, fordetermination of dialyzer clearance characteristics, or for priming ofthe blood circuit with dialysate solution. In one aspect of theinvention, a drain cassette 815 may comprise a drain chamber/air trap4703, a valve 831 on one or both of the arterial and venous blood lines,a check valve 836 in the drain line, and temperature and conductivitysensors 834, 835 into one modular component that can be readilyconnected to or disconnected from the front panel of dialysis unit 51.As shown in FIG. 21A, in an embodiment, the arterial and venous bloodlines may be connected to the drain cassette 815 via connection points814 on front panel 811. The drain cassette 815 may include a channel orchamber which merges fluid flow from the venous and arterial bloodlines, exiting via a common outlet to a drain line 31.

As noted previously, the drain cassette 815 may optionally include avalve 831 in the venous path (or, alternatively in the arterial path, orboth paths). In a preferred embodiment, the valve 831 is a pneumaticallyoperated membrane valve, which is actuated by an electromechanical valveplumbed to a pneumatic pressure source and under the control of anelectronic controller. The drain cassette 815 may also optionallyinclude conductivity and thermal probes 834, 835 in the fluid flowchannel or chamber within the housing of the cassette 815. In apreferred embodiment, the drain outlet, the pneumatic control port andthe electrical connections for the conductivity and thermal sensorscomprise paired connectors, one member of each pair rigidly attached tothe housing of the drain cassette 815, and the other member of each pairrigidly attached to the front panel 811 of dialysis unit 51 in order toallow a user to mount or dismount drain cassette 815 quickly and easilyfrom front panel 811. As with the other blood circuit components of thefront panel 511 or 811 (including dialyzer 14, blood pump cassette 13 or824, air trap 19 or 819, and arterial and venous blood lines), draincassette 815 may be configured to be readily dismountable from dialysisunit 51.

FIG. 31 shows an exemplary modular drain cassette 815. In this view, theescutcheon 825 of the drain cassette 815 includes markings identifyingthe arterial and venous line connection points 814. A handle 821anterior to the escutcheon 825 may be grasped with a single hand andturned to engage or disengage the drain cassette 815 from the frontpanel 811. Blood line connectors 802 for each of the arterial and venousblood lines are shown engaged within their respective connection portsor points 814 on the drain cassette 815.

FIG. 32 shows drain cassette 815 in an exploded view, with escutcheon825 anterior to the front wall 826 of the drain cassette 815. In thisexample, front wall 826 sealingly forms a front wall for the commonchannel or chamber 827 of the housing 828 of drain cassette 815. Acommon outlet 829 to a drain line from the channel 827 is equipped witha fluid connector 830 mounted on the back wall of housing 828, whichoptionally may include a one-way check valve (e.g., such as a duckbillvalve) to prevent fluid within the drain line from re-entering thechannel 827. A mating connector 830 a is mounted on front panel 811, andis connected to a fluid line ultimately leading to drain. Outlet 829 ispreferably positioned higher than either fluid connection points 814 aand 814 b, in order to trap and ultimately expel to drain any air thatmay be present in the arterial or venous blood lines when connected todrain cassette 815. In this regard, the fluid channel 827 may have a Ushape, with the venous and arterial blood line connectors 802 fluidlycoupling with a respective connection port 814 a, 814 b at ends of the Ushape, and the drain outlet port 829 located at the bend of the U shape.A valve 831 may be present on one or both fluid channel portions ofchannel 827 leading from connection points 814 a and 814 b. Thus, thevalve may controllably open and close fluid communication in the channel827 between the connection ports 814 and the drain outlet port 829. Inembodiments where only one valve 831 is provided in the channel 827,flow between one connection port 814 and the outlet drain port 829 maybe controlled by the valve while fluid communication between the otherconnection port 814 and the drain outlet port 829 may be permanentlyopen. In the illustrated example, a pneumatically actuated membranevalve 831 mounted on the back of housing 828 is positioned over theportion of the channel 827 a leading from venous blood line connectionpoint 814 a. A mating pneumatic connector 831 a mounted on the frontpanel 811 supplies valve 831 with positive or negative pneumaticpressure to actuate the valve, a pneumatic pressure line extending tofront panel 811 from a pneumatic pressure distribution module ormanifold located in a rear portion of dialysis unit 51. Both connectors830 and 831 may be constructed to form radial sealing engagements (e.g.,using elastomeric O-rings) with mating connectors 830 a and 831 a on thefront panel 811 in order to allow for drain cassette 815 to be pluggedinto or unplugged from front panel 811 with relative ease. Similarly, anelectrical connector 833 may be mounted on the back wall of housing 828to make electrical connections outside of channel 827 with temperatureand/or conductivity probes positioned within channel 827. Electricalconnector 833 may be constructed to form a keyed connection with amating electrical connector 833 a on front panel 811 in order tofacilitate engagement and disengagement of the connector when draincassette 815 is installed or removed from front panel 811. In someembodiments, the connections of the outlet drain port connector 830, thevalve control port connector 831 and the electrical connector 833 torespective connectors on the panel 511 may be made essentiallysimultaneously and/or in a single operation, e.g., by pushing the draincassette 815 into place on the panel 511.

FIG. 33 shows a perspective view of drain cassette front wall 826. Inwhich electrical connections are illustrated between probes 834 and 835and connector 833. In this example, probe 834 comprises a thermistor andone of a pair of conductivity sensors, extending into channel 827 todetect both fluid temperature and conductivity. Probe 835 similarlyextends into channel 827 as the second probe in a pair of conductivitysensors extending into channel 827.

FIG. 34 shows the main housing 828 of drain cassette 815, the front wall826 having been removed for clarity. Thermal and/or conductivity probes834 and 835 are shown to illustrate their positioning in a portion 827 bof fluid flow channel 827. (Each probe, although sealingly installed onfront wall 826, has an elongated element that penetrates through frontwall 826 to reside in some portion of fluid channel 827). Electricalconnector 833 is shown to be positioned in an area of housing 828 thatis outside channel 827. In an embodiment, a check valve, such as aduckbill valve 836, may be mounted within drain connector 830 (shown inFIG. 32).

FIG. 35 shows a rear perspective view of drain cassette 815. Malefluidic connector 830 is arranged to connect to a mating connector 830 aon front panel 811, which is connected to a drain line. Male pneumaticconnector 831 is arranged to connect to a mating connector 831 a onfront panel 811, which is connected to a pneumatic pressure line. Maleelectrical connector 833 is arranged to connect to a mating connector833 a on front panel 811, which carries electrical connections fromthermal and/or conductivity sensors in housing 828 to a systemcontroller in a rear portion of dialysis unit 51. Latch member 837,connected to handle 821, is arranged to insert into a keyhole of frontpanel 811 in order to engage and lock drain cassette 815 onto frontpanel 811.

FIG. 36 shows front panel 811 in which drain cassette 815 has beendismounted. Drain cassette recess 838 is arranged to accept draincassette 815. The user need only align drain connector 830, pneumaticvalve connector 831 and electrical connector 833 on drain cassette 815with their counterpart connectors 830 a, 831 a and 833 a on front panel811 and push the cassette 815 into place to make the needed pneumaticand electrical connections. Latch member 837 of handle 821 on draincassette 815 is inserted into keyhole 837 a, and handle 821 may beturned ¼ or ½ turn to lock drain cassette 815 into recess 838, resultingin an arrangement of the front panel as shown in FIG. 21B.

The modular features of drain cassette 815 advantageously allow a userto easily mount and dismount substantially all of the blood-bearingcomponents of the dialysis system (except possibly for distal portionsof drain line 31). Thus, the dialysis unit 51 may be made available foruse by more than one individual by simply swapping out the blood bearingcomponents (e.g., a blood circuit assembly and drain cassette), each setof which is assigned to each individual user. The microbiologicalbarriers afforded by the dialyzer semi-permeable membrane, by anultrafilter for incoming water or dialysate within the dialysate-sidecircuit, and by the dialysate-side disinfection procedures between eachuse of the dialysis unit 51 allow for the dialysate-side components tobe reusable among different users. Having a modular drain cassette 815along with the other modular blood circuit components allows thedialysis unit 51 to be used as conveniently in a multi-user clinicsetting as in a single-user home setting.

In accordance with another aspect of the invention, the front panel 511of the dialysis unit 51 (or other suitable component) may be arranged toaccommodate a variety of differently sized and/or shaped dialyzer units14. Different patients, and in some cases even the same patient overtime, may be prescribed different dialyzers so as to provide differenttreatment conditions. Thus, the dialysis unit 51 is preferably arrangedto operate with multiple different types of dialyzers 14. In many cases,different dialyzers 14 have different dimensions, such as the overalldiameter and/or length of the dialyzer unit. In this illustrativeembodiment as shown in FIG. 23, the front panel 511 includes a dialyzermount with a pair of “keyhole” features 520 that are arranged to engagewith a respective dialysate quick-connect fitting on the dialyzer 14.Each keyhole feature 520 includes an upper insertion area 520 a sized toreceive a portion of the quick-connect fitting and a lower flangedportion 520 b that has a width that is smaller than an overall diameterof the quick-connect fitting and that engages with a grooved area of thequick-connect fitting. So as to aid in understanding of these features,FIG. 24 shows a dialyzer 14 with quick connect fittings 14 a attached atdialysate inlet and outlet ports of the dialyzer 14. (Blood inlet andoutlet ports are located at the extreme top and bottom of the dialyzer14 shown in FIG. 24.) The quick connect fittings 14 a shown are of astandard type, and most, if not all, dialyzers 14 have dialysateinlet/outlet ports that are arranged to engage with the standard quickconnect fittings 14 a. The quick connect fittings 14 a each include aslide element 14 b that is moved to the right (as shown in FIG. 24)relative to a base 14 c to allow the fitting 14 a to be engaged with adialysate port on the dialyzer 14. When the slide element 14 b is movedto allow the fitting 14 a to be attached to the dialyzer 14, a groove 14d is closed. However, once the fitting 14 a is properly seated on theinlet/outlet port of the dialyzer 14, the slide element 14 b may bereleased, allowing a spring (not shown) to move the slide to the left asshown in FIG. 24, reestablishing the groove 14 d to the condition shownin FIG. 24. Thus, when the quick connect fitting 14 a is properlyengaged with the dialyzer 14, the groove 14 d will be present as shownin FIG. 24.

To mount the dialyzer 14 to the keyhole features 520, the quick connectfittings 14 a may be partially inserted into the upper insertion area520 a of the top and bottom keyhole features, respectively, so that thegroove 14 d of each fitting 14 a is aligned with a flange of the lowerflanged portion 520 b of the keyhole features 520. (Note that the upperinsertion area 520 of the bottom keyhole feature 520 may be made longerthan that shown in FIG. 23 to allow the accommodation of a wider rangeof dialyzer lengths.) With the grooves 14 d aligned with the flanges,the dialyzer 14 may be lowered so that the quick connect fittings 14 aare fully received into the lower flanged portions 520 b of the keyholefeatures 520.

In accordance with another aspect of the invention, one or both of thekeyhole features 520 may be adjustable so that the weight of thedialyzer 14 is shared by both lower flanged portions 520 b of thekeyhole features 520. For example, in this illustrative embodiment, thebottom keyhole feature 520 has part of the lower flanged portion 520 badjustable in vertical position relative to the top keyhole feature 520.In this way, the portion of the lower flanged portion 520 b may beadjusted in vertical position so that, with the top quick connectfitting 14 a supported by the flanged portion 520 b of the top keyholefeature 520, the movable portion of the flanged portion 520 b of thebottom keyhole feature can be moved, e.g., upwardly, so that the bottomquick connect fitting 14 a is also supported by the flanged portion 520b. Thus, the weight of the dialyzer 14 can be shared by both keyholefeatures 520. The flanged portion 520 b may be made adjustable in anysuitable way. In this embodiment, the flanged portion 520 b has a “U”shaped member 520 c that is vertically slidable along the verticalflanges and can be fixed in place by tightening a set of thumb screws.The “U” shaped member 520 c may engage the quick connect fitting 14 a sothat the “U” shaped member 520 c supports the weight (at least in part)of the dialyzer 14.

Although in the embodiment above, the dialyzer 14 is supported bykeyhole features in the front panel 511, a support arrangement for thedialyzer may be configured in other ways. For example, the upperinsertion area 520 a is not necessarily required. Instead, only flangeportions (e.g., in the shape of a “U” shaped flange having opposedflange portions) may be provided to engage the dialyzer quick connectfittings. The flange portions may be offset from the front surface ofthe front panel 511 to provide clearance for the fitting and allow theflange portions to engage with the grooves of the quick connectfittings. Also, the flange portions need not be provided in a verticalorientation as shown, but instead may be oriented at an angle to thevertical, e.g., in a horizontal arrangement. The flange portions mayhave a detent, catch, or other feature to help maintain the dialyzer inplace as well.

In accordance with another aspect of the invention, a bicarbonate, acidand/or other reagent supply device may be selectively associated withthe dialysis unit. As described above, the dialysis unit 51 requires asupply of certain chemicals to generate dialysate and/or other materialsneeded for system operation. FIG. 25 shows a reagent supply 49 used toprovide acid, bicarbonate and/or other materials to the dialysis unit52. (FIG. 21 shows the reagent supply 49 attached to theacid/bicarbonate connection point 512 on the front panel 511.) Thereagent supply 49 in this illustrative embodiment includes an E-prongconnector 491 that is arranged to mate with the acid/bicarbonateconnection point 512. As with other connections made by the user at thefront panel 511, e.g., including the blood line connections at theconnection point 514, the mating connectors may be color coded orotherwise marked to help ensure proper connections are made. Forexample, the E-prong connector 491 and the acid/bicarbonate connectionpoint 512 may be colored orange, while the arterial line 203 and itsmating connection at the connection point 514 may be colored red, andthe venous line 204 and its mating connection at the connection point514 are colored blue. Leading from the E-prong connector 491 are abicarbonate supply line 492, a water supply line 493 and an acid supplyline 494. (See FIG. 6 and the accompanying description regarding thefunction of these lines.) The water supply line 493 provides water to abicarbonate supply 28 (which in this embodiment is a 750g AltracartBicarbonate cartridge (#500750A) sold by Baxter International Inc. thatincludes a powdered bicarbonate material, but may be any suitablesupply), which provides bicarbonate to the dialysis unit 51 via thebicarbonate supply line 492. In this embodiment, the acid supply line494 leads to an acid bag spike 495, which may be used to pierce and drawa suitable acid from a IV-type bag or other container. In thisembodiment, the acid bag spike 495 includes a spike member 495 a and apair of spring clips 495 b. The spring clips 495 b are joined togetherat center portions by a connecting bar such that the spring clips 495 band the connecting bar form an “H” shape and allow the spring clips 495b to be pivoted relative to each other when proximal ends of the springclips 495 b are squeezed toward each other. The spring clips 495 b maybe arranged to engage with a connector element on an acid bag (or otheracid supply, not shown) so that the spike member 495 a remains engagedwith the bag until a user disengages the clips 495 b. For example,distal ends of the clips 495 b may include barbs that engage with theacid supply, and the clips may be disengaged from the acid supply bysqueezing proximal ends of the clips 495 b together to disengage thebarb elements at the distal ends of the clips 495 b from the acidsupply. The acid bag spike 495 may also include a valve 495 c (in thiscase, a pinch clamp) to open/close the line of the acid bag spike 495.In accordance with one aspect of the invention, the acid bag spike 495may be replaced (disconnected from the acid supply line 494 at a capconnector 496) with another component, such as an acid jug straw (notshown) or other arrangement. When used with a jug straw, the capconnector 496 may be engaged with an acid jug opening such that the capconnector 496 covers the opening, like a cap. Alternatively, the jugstraw can terminate in a spike, which then has the ability to penetratea self-sealing (e.g. rubber) membrane covering the opening of the acidjug. Thus, different types of components may be attached to the acidsupply line 494 depending on the acid supply arrangement (such as a jug,bottle, bag, or other).

FIG. 26 shows a close up view of the E-prong connector 491 and thecorresponding connection point 512 at the front panel 511. The E-prongconnector 491 has three parallel prongs (corresponding to thebicarbonate and acid supply lines 492 and 494 and the water supply line493) that that engage with corresponding receiving holes in theconnection point 512. The E-prong connector 491 and receiving holes inthe connection point 512 are arranged so that a center lumen (the watersupply line 493) is arranged above, or otherwise out of, a common planeof the two outer lumens (the bicarbonate and acid supply lines 492 and494). In this way, it is ensured that the bicarbonate and acid supplylines 492 and 494 are properly connected since the E-prong connector 491cannot be engaged with the connection point 512 unless appropriatelyoriented. The E-prong connector 491 includes a pair of spring tabs 491 athat can be engaged with corresponding slots 512 a in the connectionpoint 512, e.g., when the prongs are properly seated in receiving holesof the connection point 512. With the tabs 491 a engaged in the slots512 a, the E-prong connector 491 cannot be easily removed from theconnection point 512, helping reduce the likelihood of an accidentaldisconnection. The E-prong connector 491 may be disconnected by pressingthe tabs 491 a toward each other so that barbs at the distal ends of thetabs 491 a disengage from the slots 512 a. The connection point 512 hassimilar spring tabs 512 b which allow the connection point 512 to beconnected to and disconnected from the front panel 511.

In accordance with another aspect of the invention, a disinfectconnector (not shown) engages with connection point 512 for use during adisinfection procedure. The disinfect connector has three parallelprongs having a similar orientation as the E-prong connector 491, sothat the prongs may engage with the receiving holes in connection point512. The channels in the prongs of the disinfect connector terminatewithin a common chamber within the disinfect connector. Thus, during adisinfect procedure, the bicarbonate flow line, acid flow line and waterflow line are all interconnected, permitting disinfection of each ofthese flow lines during the disinfect procedure. (This is shown as adashed inverted “T” line at 49 in FIG. 6).

In accordance with another aspect of the invention, the blood lines 203,204 are equipped with a connector that enables two types of connectionsto be made. One type of connection is a plug-in or press-in connectionby which the connector can be pushed into a receiving lumen and aleakfree connection made without requiring rotation of the connector orthe receiving lumen. A second type of connection is a screw-typeconnection by which a leakfree connection can be made by a threadedengagement of the connector with a complementary element. For example,FIGS. 27 and 28 show a perspective view and a side view of a blood lineconnector 202 that is used with the blood lines 203, 204 and that canengage with the blood line connection point 514 on the front panel 511.The connector 202 includes a tube connection end 202 a that connects tothe corresponding blood line 203, 204, and a patient access connectionend 202 b that is arranged to connect to both a patient access as wellas the connection point 514 to establish a leakfree connection. At thepatient access connection end 202 b, the connector 202 includes afrustoconical member 202 c that has an internally threaded portionarranged to engage with an externally threaded patient access. Forexample, the frustoconical member 202 c may be part of a male-type luerconnector that includes the central tube 202 e extending from the centerof the frustoconical member 202 c. When making the luer connection, thetube 202 e may extend into a female luer connector at the patient accessand the threaded portion on the interior of the frustoconical member 202c may engage with a thread on the female luer connector of the patientaccess (whether arterial or venous). Such luer connections are standardwhen connecting blood lines to a patient access. However, the connector202 may also be engaged with the connection point 514 by simply pushingthe patient access connection end 202 b into a receiving hole of theconnection point 514. When making this connection, the exterior of thefrustoconical member 202 c may engage with a suitable seat, or othersurface or element in the connection point 514 (such as a valve seat,O-ring, or other) so that a seal is formed between the frustoconicalmember 202 c and the connection point 514. The central tube 202 e mayalso, or instead, be used to engage with the connection point 514 toestablish a suitable seal. Locking arms 202 d that extend rearwardlyfrom the frustoconical member 202 c may engage with holes 514 a in theconnection point 514 (e.g., barbed portions on the arms 202 d may engagewith the holes 514 a) to help maintain the connector 202 in thereceiving hole of the connection point 514. The connector 202 may bereleased by pressing the arms 202 d toward each other (e.g., by pressingon finger depression portions at the distal ends of the arms 202 d),thereby disengaging the barbs from the holes 514 a, and withdrawing theconnector 202. Note that the connection point 514 may include springtabs 514 b to allow the connection point 514 to be selectivelyengaged/disengaged at the front panel 511. The connectors 202 may bemade in any suitable way, such as by molding of plastic as a singleunitary part.

FIG. 29 shows a perspective view of a blood circuit assembly 17 in analternate embodiment. This embodiment is different from that shown inFIGS. 18 and 19 in a few ways. For example, in this embodiment, theblood lines 203 and 204 have a cross section having a shape similar to a“figure 8” in which one portion of the “figure 8” includes a lumen tocarry blood or other fluid, and another portion of the “figure 8”carries a conductor. That is, the blood lines 203 and 204 include alumen through which blood and other fluids may flow, and another lumenthrough which an electrical conductor may pass. Further detail regardingthis and other arrangement is provided below with reference to FIGS.37-49. As also discussed in more detail below, the electrical conductormay be used to detect disconnection of a blood line 203, 204 from apatient or other connection point. Additionally, the organizing tray 171in FIG. 29 is different from that shown in FIG. 19 in that theengagement members 174 may include a slot or hole that the blood lines203, 204 are engaged with, but in this embodiment, the engagementmembers 174 need not engage the blood lines 203, 204 so as to resistpulling of the lines 203, 204 downwardly, e.g., for mounting the linesin an occluder. Instead, in this embodiment, the blood lines 203, 204may be allowed to move freely with respect to the engagement members174. Another modification in the embodiment is that the engagementmembers 174 include a push plate that spans across both lines 203, 204.This is in contrast to the arrangement in FIG. 19 where each line 203,204 is engaged by engagement members 174 that are independent of eachother. The arrangement in FIG. 29 may provide an advantage in someembodiments that allows a user to engage the lines 203, 204 with respectto slots 517 that lead to an occluder in an single operation. (See FIG.22) In one embodiment, the slots 517 may each be associated with an airdetector that operates to detect whether there are air bubbles in thelines 203, 204 (e.g., by optical detection or other so that air in aline 203 or 204 can be detected by a respective air detector in one ofthe slots 517). Thus, the engagement members 174 may function toassociate the lines with an air detector or other feature in additionto, or instead of, an occluder or other arrangement that positions thelines 203, 204 in a desired way. In this embodiment, the engagementfeatures 174 include slots arranged on an underside of the push platethat engage with a narrower portion of the lines 203, 204 (e.g., theportion that carries the electrical conductor) so as to position theconductor near the push plate. This may help position the lines 203, 204in the slots 517 in such a way that the conductor does not interferewith an air detector operating to detect air in the lines 203, 204. Asmentioned above, the slots on the push plate that engage with the lines203, 204 may engage the lines so that the lines do not rotate relativeto the push plate, but are allowed to move along their length relativeto the push plate. FIG. 30 shows a closeup view of a portion of theblood circuit assembly of FIG. 29 and illustrates how a portion of theorganizing tray 171 may be arranged to at least partially conform to theshape of a blood line 203, 204 held by the tray 171. Similar to theengagement members 174, the tray 171 portions that engage with the lines203, 204 may be arranged to orient the lines 203, 204 so that theconductor portion of the line faces outwardly. This may help properlyposition the lines 203, 204 for the engagement members 174 or otherportions of the assembly 17.

It should be understood that any and all of the aspects of inventiondescribed herein may be combined with or otherwise incorporated with anyof the other aspects of invention and/or embodiments described. Forexample, a dialysis system incorporating one or more aspects ofinvention described herein may include a line disconnection functionlike that described in connection with FIGS. 37-49. Such a disconnectionfunction may include features such as 1) an electrical circuit or othersuitable circuitry to detect a change in voltage, resistance or othercharacteristic indicative of a disconnection of a blood line 203, 204with respect to an associated connector, 2) positioning of detectionelectrodes suitably near a patient or other reference, 3) one or moreconnector arrangements, 4) blood line tubing arrangements or othersuitable arrangements in which a blood line carries both a fluid flowlumen and an electrically conductive feature, and so on. For example, inone aspect of the invention, a blood circuit assembly may include bloodlines, one or more blood pumps, an air trap and electrical circuitrycomponents suitable for use in detecting disconnection/connection of oneor more blood lines on an organizing tray. Such an arrangement may allowa user to make several different connections, whether fluidic, pneumaticand/or electrical, in a relatively uncomplicated and straightforwardway.

Accordingly, aspects of the invention relate generally to systems andmethods to detect disconnection of an indwelling vascular line beingused in a dialysis treatment, such as a catheter or needle, or itsattached tubing. If not quickly detected, a disconnection can lead torapid exsanguination, particularly when the blood in the catheter ortubing is under positive pressure. Examples of circumstances involvingpositive intravascular pressure include the positive pressure associatedwith an artery or arterio-venous fistula, or the positive pressureassociated with an extracorporeal blood pump circuit. In hemodialysis,for example, a blood pump can generate blood flow rates of 400-500ml/min, making rapid, reliable disconnect detection particularlydesirable. Indeed any medical treatment involving relatively high flowor high pressure extracorporeal circulation (such as, for example,hemoperfusion or cardiopulmonary bypass) can be made safer by having aneffective system to monitor the integrity of the arterial (withdrawal)and venous (return) blood lines.

In hemodialysis, for example, extracorporeal blood circulation can beaccomplished with vascular access using either a single indwellingcatheter, or two separate indwelling catheters. In a single cathetersystem, blood is alternately withdrawn from and returned to the body viathe same cannula. A disconnection in this system can be quickly detectedby placing an air monitor in the line at or near the pump inlet, becauseair will be drawn into the line from the disconnection site during theblood withdrawal phase of the pumping. On the other hand, in atwo-catheter system, blood is typically continuously withdrawn from thebody via one catheter inserted in a blood vessel or fistula, andreturned to the body via the second catheter inserted in the same vesselsome distance from the first catheter, or in a separate blood vesselaltogether. In the two-catheter system, it is also possible to monitorfor catheter or tubing dislodgement in the blood withdrawal or‘arterial’ segment by using a sensor to detect the presence of air beingentrained into the arterial tubing as blood is withdrawn from the bloodvessel under negative pump pressure and/or positive fistula pressure.However, air-in-line detection cannot reliably detect a disconnection ofthe venous (return) segment of the extracorporeal circuit. In this case,if the blood-withdrawal path remains intact, air will not be introducedinto the line. Thus it is particularly important to be able to detect adisruption in the continuity of the return line from the extracorporealpump to the vascular access site.

In one aspect, the invention comprises a system for detecting whether avascular access device, such as a needle, cannula, catheter, etc.becomes disconnected or dislodged from a blood vessel or vascular graft.The system includes a fluid delivery device that provides for the flowof a liquid through a tube or conduit into the blood vessel via anindwelling needle or catheter at a first site on the blood vessel orgraft. The fluid may be an electrolyte solution or other solutionsuitable for intravenous infusion, or it may be blood or bloodcomponents. An electrode is disposed to be in contact or fluidcommunication with the lumen of the conduit, and a second electrode isdisposed to be in fluid communication with blood within the blood vesselor graft via a second on the blood vessel or graft. An electroniccircuit is connected to the first and second electrodes, and configuredto deliver a control signal to the first and second electrodes in orderto measure the electrical resistance of the fluid between the first andsecond electrodes, such that at least one of the electrodes is locatedcloser to the blood vessel or graft than to the fluid delivery device.In some embodiments the electrode is located at about 50-70% of thedistance from the fluid delivery device to the blood vessel or graft. Inother embodiments, the electrode is located at about 70-90% or more ofthe distance from the fluid delivery device to the blood vessel orgraft. The fluid delivery device can include a pump, either for blood orfor other therapeutic or diagnostic fluid. The fluid delivery device canbe part of a hemodialysis blood flow circuit, which may or may notinclude a blood pump, a dialyzer cartridge, or an air trap andassociated tubing. The second electrode may be placed in contact withthe lumen of a second conduit or tube that is in fluid communicationwith the blood vessel or graft at the second site. The second conduitmay form part of a fluid flow path from the blood vessel or graft to thefluid delivery device. The fluid in the second conduit may be bloodbeing delivered to an extracorporeal blood flow circuit.

The system may comprise a first and second connector connecting a pairof vascular access catheters accessing a blood vessel segment orvascular graft segment at two different sites. The first and secondconnectors may each connect to a flexible tube leading to the fluiddelivery device. Each connector may include an electrode that is exposedto the lumen of the connector. A wire may be attached to each connector,the wire being connectable on its other end to the electronic circuit.The flexible tubes may be double lumen tubes having a first lumen forcarrying fluid and a second lumen for carrying a wire. The wires of eachtube may be connected on the other end of the tube to a connector forconnection to the electronic circuit.

The electronic circuit or an associated microprocessor may be configuredto convert the voltages measured across terminals connected to theelectrodes by the electronic circuit into resistance values. The systemmay comprise a controller configured to receive a signal from theelectronic circuit or microprocessor, the signal representing theelectrical resistance between the electrodes, the controller beingprogrammed to trigger an alert signal when the electrical resistancevalue exceeds a pre-determined threshold. The alert signal may be anaudible or visual signal to the person whose blood vessel is beingaccessed, and optionally an alert signal may include an electricalcommand to a tubing occluder apparatus. The tubing occluder apparatusmay be actuated to mechanically occlude one or more of the tubes leadingfrom the vascular access sites. The tubing occluder may operate in anumber of ways, such as, for example electromechanically, hydraulically,or pneumatically.

In another aspect, the invention comprises an apparatus for monitoringthe continuity between a vascular access device and a blood vessel orvascular graft segment, comprising, a first and second vascularconnector, the first connector being attached on a proximal end to adistal end of a fluid-carrying lumen of a first double-lumen tube, andthe second connector being attached on a proximal end to a distal end ofa fluid-carrying lumen of a second double-lumen tube. The firstconnector comprises a first electrode in contact with a lumen of thefirst connector and electrically connected to a wire within awire-carrying lumen of the first double-lumen tube, and the secondconnector comprises a second electrode in contact with a lumen of thesecond connector and electrically connected to a wire within awire-carrying lumen of the second double-lumen tube. The wire within thefirst double-lumen tube and the wire within the second double-lumen tubeare each connected to an electrical connector at a proximal end of thedouble-lumen tubes. The distal end of each connector may be configuredwith a locking feature to provide a reversible, air-tight connectionbetween the connector and a mating connector of a vascular catheter. Theproximal end of the double-lumen tubes can be connected to a blood pumpon an arterial side, and an air trap on a venous side; and in ahemodialysis system, the blood pump and air trap may each be reversiblyconnectable to a dialyzer cartridge.

In another aspect, the invention comprises a vascular connectorcomprising a proximal fluid connection end, a distal fluid connectionend, and an electrode configured to electrically connect afluid-carrying lumen of the connector with a wire external to thevascular connector. The proximal end of the connector may be configuredto connect with a flexible tube, and the distal end of the connector maybe configured to connect with a mating connector of a vascular catheter.The electrode may be installed in a conduit on the connector thatconnects the lumen of the connector to the exterior of the connector.The electrode may be lodged into the conduit in a manner to provide anair-tight seal between the lumen and the exterior of the connector. Anelastomeric member such as an O-ring may be installed between theelectrode and the conduit to contribute to the air-tight seal.

In another aspect, the invention comprises an electrical circuit formeasuring the resistance of a liquid between a first and secondelectrode, the first electrode connected to a first terminal of theelectrical circuit, and the second electrode connected to a secondterminal of the electrical circuit, comprising a capacitor C1 connectedon a first end to the first terminal and a capacitor C2 connected on afirst end to the second terminal; a known reference resistance Rrefconnected on a first end to a second end of capacitor C1; switchingmeans for connecting either (a) a first reference voltage V+ to a secondend of Rref, and a lower second reference voltage V− to a second end ofC2 to form a first switch configuration or; (b) the first referencevoltage V+ to the second end of C2 and the lower second referencevoltage V− to the second end of Rref to form a second switchconfiguration; and measuring means for measuring a voltage Vsense at theconnection between C1 and Rref; such that the electrical circuit isconfigured to determine the value of the resistance of the liquid basedon the known reference resistance Rref and the observed voltage Vsensefor each of the first and second switch configurations. The resistanceRref may be chosen to be a value that permits conductivity measurementof an electrolyte solution or other solution suitable for intravenousinfusion. The electrolyte solution may include dialysate solution. Theresistance Rref may also be chosen to permit measurement of theresistance of a volume of blood between the first and second electrodes.

Conductivity Circuit

An exemplary electrical circuit shown in FIG. 37 can be used to measurethe electrical conductivity or resistance of a subject fluid. In oneembodiment, the fluid may be an electrolyte solution or dialysate fluid,and the circuit may ultimately provide a measurement of the conductivityof the fluid to ensure its compatibility for intravascularadministration. In addition to monitoring the concentration of dissolvedsolutes in the fluid, the electrical circuit can also monitor for anyinterruption in the continuity of the fluid between the electrodesconnected to the circuit. For example, it can be used to monitor anintravenous fluid line for the presence of air bubbles, or for thepresence of a contaminating substance. In another embodiment, the fluidmay be blood, and a change in the measured electrical resistance of ablood flow path (for example, in a conduit) may be used to indicate if adiscontinuity occurs between the blood flow path and measuringelectrodes. For example, the blood flow path may comprise a column ofblood between two electrodes that includes indwelling needles orcatheters in a segment of a blood vessel, arterio-venous fistula orgraft. Vascular access disconnection can result in the introduction ofair into the blood flow path, causing a change in the resistivity of theblood column between the electrodes. The electrical circuit can bereadily modified (depending on its application) to adjust for thedifference between the impedance of a blood flow path and that ofdialysate fluid.

The circuit shown in FIG. 37 may be used to measure an unknownresistance Rx of a subject media 1 using inexpensive electroniccomponents, particularly where the unknown resistance involves aconductive path through an electrolytic fluid. A switching network 2comprising a pair of multiplexers allows the connection of nodes VA andto reference voltages V+ and V−. The subject media 1 having unknownresistance Rx is connected to terminals VTA and VTB 3, and forms avoltage divider with reference resistor Rref 4. To make a conductivitymeasurement, alternating voltages can be presented to the subject media1 via switching network 2 to the voltage divider created by the knownreference resistor Rref 4 (680 ohms, for example, in the case ofdialysate fluid) and the unknown resistance Rx of the subject media 1.The midpoint of the voltage divider is measured. The signal Vsense atpoint 8 is buffered by amplifier 10 to make the input signal Vin of theanalog-to-digital converter (ADC) 111. Vsense switches between twovalues as the voltage divider is driven first one way and then the otherway. This signal is valid only for a short period of time afterswitching because the fluid in the conductivity cell 1 is AC coupledinto the circuit through capacitors C1 and C2 6. Thus DC-blockingcapacitors C1 and C2 6 may be used to prevent DC currents from passingthrough the unknown resistance (which may include a conductive paththrough electrolytic fluid or blood). In an embodiment, seriescapacitors C can each comprise two capacitors in parallel, one having avalue, e.g., of 0.1 uF, and the other having a value, e.g., of 10 uF.Series resistors 7 may be used to reduce exposure by the switch networkand other sense circuitry to noise and surge voltages. ADC 111 can takemultiple samples of the signal as the circuit is switched between thetwo configurations.

The switching network 2 can be driven by a pair of alternating binarycontrol signals 131, 144 that connect VA to V+ and VB to V− during onehalf-cycle, and VB to V+ and VA to V− during the other half-cycle. Thisresults in a waveform at the Vsense node 58 that is similar to thewaveform 20 shown in FIG. 38. In this embodiment, Vref is 4 volts,resulting in a Vsense amplitude of less than 4 volts, as shown in FIG.38. A voltage divider 8 creates the voltages V+ and V− that are near thepositive reference voltage Vref and near ground, respectively. In oneembodiment, R1 can have a value of 10 ohms, and R2 can have a value of2K ohms When both multiplexers of switching network 2 are commanded tozero, the circuit is at rest and the lower voltage is presented toterminals VTA and VTB 3. When VA is high and VB is low, the highervoltage is presented to the reference resistor Rref 4 and the lowervoltage is presented to the subject media 1 having unknown resistanceRx. When VB is high and VA is low, the higher voltage is presented tothe subject media 1 having unknown resistance Rx and the lower voltageis presented to the reference resistor Rref 4.

A change in voltage ΔVsense before and after each square wave edge, canbe shown to depend only on the reference resistance Rref 4, the unknownresistance Rx of subject media 1, and any series resistance (including,e.g., Rs 7), and is generally independent of series capacitance C1 or C26, since during this short time period the capacitor acts as anincremental short circuit. In particular,

Δα=ΔVsense/(V+−V−)=(Ry−Rref−Rth)/(Ry+Rref+Rth)=(ρ−1)/(ρ+1)

where Ry=Rx+2Rs+Rth, where Rth=source series resistance from multiplexer2 and voltage divider 8, and ρ=Ry/(Rref+Rth). (Source series resistanceRth, can be derived as the sum of the resistance of multiplexer 2 andthe Thevenin equivalent resistance of the voltage divider 8. Forexample, for R1=10 ohms, R2=2K ohms, then Rth=R1.parallel.(R1+R2)=9.95ohms). Thus, if Ry is a short circuit, then ρ=0 and Δα=−1. The sensenode's change in voltage ΔVsense is then equal to the voltage change atVB which has an amplitude opposite to the drive node at VA. If Ry is anopen circuit, then ρ=∞ and Δα=1. The sense node's change in voltageΔVsense is then equal to the voltage change at the drive node VA.Accordingly, if this change in voltage is measured, the precedingequations can be solved for the unknown resistance Rx:

Rx=ρ(Rref+Rth)−2Rs−Rth, where ρ=(1+Δα)/(1−Δα)

As shown in FIG. 37, a low-pass filter 9 can be formed by resistor Rfand capacitor Cf, to filter out high-frequency noise. In one exemplaryarrangement, Rf can have a value of 1K ohms, and Cf can have a value of0.001 uF. Buffer amplifier 10 and analog-to-digital converter (ADC) 111can then measure the sensed voltage for a computer or digital signalprocessor (not shown).

The reference voltages V+ and V− may be advantageously derived from avoltage divider 8 so that V+ is close to the reference voltage Vref ofthe ADC 111, and V− is close to the ground reference voltage of the ADC111. For example, for R1=10 ohms, R2=2 kohms, and Vref=4.0V, thenV+=3.980V, and V−=0.020V. This places both voltages within but near theedges of the active sensing region of the ADC 111, where they can beused for calibration (discussed below). Switch SW1 12 may be used tohelp calibrate the load resistance sensing.

Several improvements may decrease errors related to variations ofcomponent values. First, a calibration step can be introduced where VAis switched to V+ for a relatively long period of time, until settlesand is approximately equal to V+, at which point ADC 111 can take ameasurement of Vsense. A second calibration step can involve switchingVA to V− for a relatively long period of time, until Vsense settles andis approximately equal to V−, at which point ADC 111 can take anothermeasurement of Vsense. This allows the ADC 111 to measure both V+and V−.

Secondly, as shown in FIG. 38, while the square wave is switching, ADC111 readings before and after both edges of the switching waveform maybe used to compute the dimensionless quantity Δα:

Δα=ΔVsense/(V+−V−)=[(V2−V1)+(V3−V4)]/2(V+−V−)

As a result, both edges of the waveform can be used to measureΔVsense=[(V2−V1)+(V3−V4)]/2, so that asymmetric responses to the circuitare likely to be canceled out. Alternatively, an average voltage atabout the midpoint of the waveform may be used; so that, for example,Δα=ΔVsense/(V+−V−)=[(V7−V6)+(V7−V8)]/2(V+−−V−), andΔVsense=[(V7−V6)+(V7−V8)]/2. In addition, only differential measurementsof the input signal Vin of the ADC 111 can be used. Thus, any offseterrors of the buffer amplifier 10 and ADC 111 can be canceled out. Also,Δα is a ratiometric quantity based on measurements using the same signalpath. Thus, any gain errors of the ADC 111 can also be canceled out.

The reference resistor Rref 4 may be optimally chosen to be equal to thegeometric mean of the endpoints of the desired range of unknownresistances, taking series resistances Rs 7 into account. For example,if Rs=100 ohms and Rx varies from 100 ohms to 3000 ohms, then Ry=Rx+2R,varies from 300 ohms to 3200 ohms, and Rref should be approximately thesquare root of (300 ohms3200 ohms)=980 ohms. To measure an unknownresistance in the range of 100 k-300 k ohms (as in, for example, acolumn of blood extending from one electrode to another via anarterio-venous fistula), the reference resistor Rref 4 can be changed toapproximately 200 k ohms and the filter capacitor Rf of low pass filter9 at the input to the buffering amplifier 10 can be removed completely.

Because a voltage divider's output is a nonlinear function of itsresistance ratio, errors or noise in readings from the ADC 111 producetheir lowest fractional error (sensitivity) in the resultant calculationof Ry when it is equal to Rref, and the sensitivity increases the moreRy diverges from the reference resistance Rref. Specifically, it can beshown that the sensitivity in resistance ratio is as follows:

Sρ=(1/ρ)Δ ρ/ΔΔα=2/[(1+Δα)(1−Δα)]=2/[1−−(Δα)²]

When Ry=Rref, ρ=1, Δα=0 and Sρ=2. Thus, for a change in Δα of 0.001(0.1% of the ADC full-scale) around this point, the calculatedresistance Ry changes by 0.002 or 0.2%. The sensitivity increases as ρdiverges from 1, as shown in Table 1.

TABLE 1 P Δα Sρ 1 0 2 2, 0.5 .+−.0.333  2.25 4, 0.25 .+−.0.6  3.13 5.83,0.172 .+−.0.707  4 10, 0.1 .+−.0.818  6.05 20, 0.05 .+−.0.905 11.03

FIG. 39 shows that the noise/error sensitivity doubles at about a 6:1ratio of unknown/reference resistance, and triples at a 10:1 ratio.Resistance measurements outside this range may suffer in their increasedsensitivity to noise and error.

For calibration purposes, a switch SW1 12 can be used to make resistancemeasurements to calibrate out a point at Rx=0. Preferably this switch 12should be placed across the terminals VTA and VTB 3, or as close to theterminals as feasible, which would give a true zero-point calibration.In practice, however, locating the switch 12 close to the terminals VTAand VTB 3 may make the switch 12 prone to external noise and surgevoltages, and may introduce DC leakage current into the subject media 1.

The series capacitances C1 and C2 6, and the use of square waves areimportant for unknown resistances that include an electrolyticconductive path. There are at least two reasons for this. First, it maybe important in many applications to prevent DC current from flowingthrough an electrolyte solution or a bodily fluid having similarproperties; otherwise electroplating and/or electrolysis of electrodesat the terminals VTA and VTB 3 can occur. In this circuit, thecapacitors C1 and C2 6 block DC currents. Furthermore, because thecapacitors may allow very small currents to flow (microamps or less),using an alternating square wave voltage may help to limit the averagecurrent further.

Secondly, in the event that a small electrochemical DC voltage isinduced in the subject media 1 (for example, the electrodes in a fluidpath may oxidize over time at different rates), this DC voltage can beblocked by the capacitors C1 and C2 6. Because the method forcalculating resistance takes differential measurements, any residual DCvoltage may be canceled out through the process of calculating theunknown resistance Rx of subject media 1.

Vascular Disconnect Detector

With the appropriate modifications of a conductivity measurement circuitsuch as the one described above, it is possible to detect theconductivity and changes in the conductivity of blood. Morespecifically, it is possible to detect the change that occurs in theconductivity of a volume of blood when air enters the volume. Thissituation can occur, for example, when an intravascular access sitebecomes dislodged in an extracorporeal blood circuit.

The circuit shown in FIG. 37 can be used to measure the resistance of avolume of fluid in a conductivity cell or conduit 1. For measurements ofRx of a conductivity cell 1 representing the resistance or conductivityof a volume of dialysate solution, a convenient value for the referenceresistor Rref 4 can be chosen to be approximately 680 ohms. Formeasurements of Rx of a conduit 1 representing the resistance orconductivity of a column of blood extending from a first cannula orneedle, through an arterio-venous fistula, to a second cannula orneedle, a convenient value for the reference resistor Rref 4 can bechosen to be approximately 200 k ohms.

The advantages of using this circuit to monitor the continuity of acolumn of a bodily fluid such as blood or plasma include the following:Capacitive coupling to the conductivity cell or conduit 1 blocks DCcurrent which could cause plating and corrosion of electrodes atterminals VTA and VTB; Voltages and current levels are very low anddecoupled for patient safety; Current only flows briefly while themeasurement is being taken. No current flows between measurements.

With the lower reference resistor Rref 4 value (e.g. 680 ohms), thiscircuit is appropriately configured for dialysate conductivitymeasurements. With a much higher reference resistor Rref 4 value (e.g.200 k ohms) this circuit is appropriately configured for measuring theresistance between an arterial needle and a venous needle to detectvascular needle dislodgement from an arterio-venous fistula.

Electrode Placement

The continuity of a fluid column leading from a fluid delivery apparatusto a patient's blood vessel or vascular graft can be monitored using theelectronic circuit described above. The fluid being delivered mayinclude blood or any electrolyte solution, including dialysate fluid.Although the following discussion will involve a hemodialysis system,the same principles of operation of the invention can apply to anydevice that is configured to deliver a fluid to a patient via a vascularaccess. In an embodiment illustrated by FIG. 40, the conductivity of avolume of blood or other fluid within a fluid flow circuit 100 of ahemodialysis machine 200 can be monitored electronically, usingelectrodes on each end of the volume that make direct contact with theblood or other fluid. Using an electrical circuit such as the one shownin FIG. 37, one electrode can be connected to the VTA terminal, and theother electrode can be connected to the VTB terminal of the circuit. Thevoltages applied to the electrodes by the circuit can be sufficientlysmall (e.g., about 4 volts or less), sufficiently brief, and with DCvoltages sufficiently decoupled so as to prevent any harm to thepatient. In this example, a fluid flow circuit 100 is shown, includingan arterial access needle 102, an arterial catheter tubing 104, anarterial catheter tubing connector 106, arterial blood circuit tubing108, a transition 110 between the blood circuit tubing 108 andhemodialysis machine 200, a blood pump inlet line 112, a blood pump 13,a blood pump outlet line 116, a dialyzer 14, a dialyzer outlet line 120,air trap 122, a transition 124 between hemodialysis machine 200 andvenous blood circuit tubing 126, a venous catheter tubing connector 128,a venous catheter tubing 130, a venous access needle 132, and theintraluminal volume of that portion of the patient's blood vessel orfistula 134 that lies between the arterial access needle 102, and thevenous access needle 132. It should be noted that the inventiondescribed herein also encompasses circumstances in which the arterialaccess needle may reside in one blood vessel of a patient, while thevenous access needle may reside in a separate blood vessel some distanceaway from the arterial access site. Furthermore, the circuit describedabove may be used to monitor the integrity of a vascular access in afluid delivery system that does not have the venous return line shown inFIG. 40. In that case, for example, an electrode at location B could bepaired with an electrode in contact with fluid in a dead-end linecommunicating with a second needle or cannula accessing the blood vesselor vascular graft. In another example, an indwelling hollow cannula orsolid trocar in the vascular segment can be equipped with a conductivewire which could then serve as the second electrode in the monitoringsystem. The vascular segment being accessed may be a surgicallyconstructed arterio-venous fistula, and may also include an artificialconduit such as a GoreTex® vascular graft. The term ‘arterial’ is usedherein to denote the portion of the blood flow circuit that conductsblood away from the patient and toward the hemodialysis machine 200. Theterm ‘venous’ is used to denote the portion of the blood flow circuitthat conducts blood away from the hemodialysis machine 200 and backtoward the patient. The term ‘access needle’ is used to denote a needleor catheter device that penetrates the patient's vascular segment orfistula. In different embodiments it may be permanently fused orreversibly connected to a corresponding catheter tubing 104, 130.

The continuity of any segment of the fluid flow circuit 100 can bemonitored by positioning two electrodes in contact with the fluid oneither side of the fluid and blood-containing segment of interest. Inorder to monitor for a disconnection of the arterial access needle 102,or the arterial catheter tubing 104, or the venous access needle 132 orvenous catheter tubing 130, one electrode can be placed in continuitywith the lumen of the venous side of the blood flow circuit, while asecond electrode is placed in continuity with the lumen of the arterialside of the blood flow circuit. In one embodiment, the two electrodescan be positioned on or near the dialysis machine 200, with an electrodein contact with blood upstream of blood pump 110, and a second electrodein contact with blood downstream of the dialyzer 14 and/or air trap 122.For example, the electrodes can be incorporated into transitionlocations 110 and 124.

In another embodiment, one of the electrodes can be positioned to be incontact with the fluid in the fluid flow circuit 100 at a point that iscloser to the vascular access site 134 than it is to the equipment (e.g.a dialysis machine) used to deliver fluid flow to the accessed bloodvessel or vascular graft. In a preferred embodiment, both electrodes canbe positioned to be nearer to the patient's blood vessel or vasculargraft than the equipment associated with the dialysis machine 200. Thismay further reduce electrical interference associated with the dialysismachine 200. An electrode A can be conveniently placed at or near thearterial catheter tubing connector 106 and a second electrode B can beconveniently placed at or near the venous catheter tubing connector 128.In this arrangement, the electrical continuity pathway from the firstelectrode through the patient's vascular access to the second electrodeis much shorter—and the electrical resistance lower—than the pathwayextending back toward the dialysis machine 200. In some cases, theaccess catheters 104 and 130 can be as short as about a foot, whereasthe arterial and venous tubings 108 and 126 can be about six feet long.Because of the electrical conductive properties of the fluid in thecircuit, the electrical resistance associated with the pathwayincorporating tubing 108 and 126, and components of the dialysis machine200, can be many times greater than the electrical resistance associatedwith the pathway through the patient's blood vessel or fistula 134.

Electrical interference associated with the dialysis machine 200 is thusreduced, and a change in electrical resistance due to an access-relateddisconnection can more easily be detected. Preferably, the electrodes Aand B are positioned to be more than 50% of the distance from thedialysis machine to the patient. More preferably (and moreconveniently), the electrodes A and B are located near the lastdisengageable fluid connection before reaching the patient. In oneembodiment of a hemodialysis system, the blood tubing 108 and 126 isapproximately 6 feet in length, and the arterial and venous cathetertubes 104, 130 are about two feet or less in length. A convenientlocation for electrodes A and B would then be at the arterial line andvenous line connectors 106, 128 (which can be, e.g. Luer type connectorsor modifications thereof) that connect the arterial and venous bloodcircuit tubes 108, 126 with the arterial and venous catheter tubes 104,130.

Connector Electrodes

As shown in FIGS. 41A and 41B, in one embodiment, a blood line connectorfor the blood circuit of a hemodialysis system may incorporateelectrodes that can make contact with any liquid within the lumen of theconnector. In one aspect, the electrode can comprise an annularconductive cap 310 placed at the tube-connection or proximal end 302 ofany suitable connector, such as, for example connector 300. Theelectrode is preferably constructed from a durable and non-corrosivematerial, such as, for example, stainless steel. The distal coupling end304 of connector 300 can be constructed to make a sealing engagementwith a corresponding Luer-type connector of an arterial or venouscatheter, for example. The inner annular surface 312 of the cap 310—inpart or in whole—can make contact with any liquid present within thelumen 314 of the connector. As shown in FIG. 41B, an O-ring 316 or asuitable sealant can be placed between the cap electrode 310 and theproximal end 302 of the connector to maintain a fluid-tight connectionbetween the connector and any flexible tubing attached to the connector.

An elastomeric O-ring may be particularly useful in hemodialysis orother extracorporeal systems in which the blood-carrying components aresubjected to disinfection or sterilization using heated liquids. Thethermal coefficients of expansion of the plastic components of aconnector may be sufficiently different from that of an incorporatedmetal electrode that a permanent seal may not be preserved after one ormore sterilization or disinfection procedures. Adding an elastomericcomponent such as an O-ring at the junction between an electrode and theconnector seat on which it is positioned may preserve the seal byaccommodating the different rates of expansion and contraction betweenthe electrode and the connector.

As shown in FIG. 42, in one embodiment, a conductive electrode 310(constructed of, e.g., stainless steel) can be incorporated into aportion of a connector 300 (either at its proximal end 302, oralternatively at its distal connecting end 304), over which the end of aflexible tubing 318 can be placed. In this embodiment, the electrode 310is generally cylindrical, and has a taper 320 on a proximal end topermit an easier slip-fit attachment of the end of a segment of flexibletubing 318 over the outside surface of the electrode 310. As shown inFIG. 42, the internal surface of the electrode 310 has an internal ledge322 that allows the electrode cap 310 to slip over and abut a proximalend 302 of connector 300. Connector 300 can be constructed of anysuitable hard material, including metal or more typically a plasticmaterial. The ledge 322 helps to ensure that a smaller diameter innersurface 312 of electrode 310 is properly positioned to make contact withany liquid (e.g. blood) that passes through the lumen 314 of connector300. The connections between connector 300 and electrode 310, andelectrode 310 and the termination of an overlying flexible tubing 318can be made air tight or permanent with any suitable adhesive compatiblewith the compositions of the components.

To ensure a more secure seal to prevent blood leakage between theconnector and electrode, and to limit the area under the electrode whereblood elements may migrate and become lodged, an O-ring 316 can beincorporated into the inner surface of electrode 310 near the electrodeinternal ledge 320. This is seen in enlarged detail in FIG. 42. In thisexample, the O-ring 316 seals between the stainless steel electrode 310and the distal end 302 of connector 300. A barb element 324 on theproximal end 302 of connector 300 can be incorporated in the connectordesign in order to hold the stretched end of the flexible tubing 318onto the proximal end 302 of connector 300. In an embodiment, theelectrode 310 is held in place by the portion of the flexible tube thatis stretched over both the electrode 310 and the barb 324 of connector300.

A wire 326 can be soldered, welded or otherwise secured onto the outersurface of electrode 310, and can travel under the overlying stretchedtubing 318 until exiting more distally along the connector 300. The wirecan thus conduct electrical signals to and from the electrode 310 as theinternal surface 312 makes contact with the intraluminal fluid (e.g.blood). In the example shown, wire 326 is soldered to a distal portionof electrode 310 and travels under tubing 318, to emerge at the abutmentof tubing 318 with a corresponding stop 326 of connector 300.

In another embodiment as shown in FIGS. 43A-43C, a connector 400 asdescribed in U.S. Patent Application Publication No. 2010/0056975 (thecontents of which are hereby incorporated by reference) has beenmodified so that a mid-portion 406 of the connector 400 can incorporatean electrode. Placement of the electrode along the mid-portion 406 ofthe connector 400 avoids having to alter the distal coupling end 404 ofthe connector, and avoids any alteration of the interaction between thetermination of the flexible tubing and the proximal end 402 of theconnector. In this example, the blood line connector 400 is constructedto make two different types of sealing connections on its distalcoupling end 404, including an internal screw-type connection 405 for aLuer-type connector of a patient access line, and an external press-intype connection 407 with a dialysis machine port for recirculation ofpriming and disinfecting fluid through the blood carrying components ofa dialysis system. The press-in feature 407 is formed having afrustoconical shape on the outside surface of the distal end 404 of theconnector 400, while the Luer-compatible screw-type feature 405 isformed on the corresponding internal surface of the distal end 404 ofthe connector 400. The outside surface of the frustoconical member isconstructed to make sealing engagement with the seat of a matingconnector of a dialysis machine 200 or other device. A pair of lockingarms 408 extending proximally from the distal coupling end 404 of theconnector 400 can each have a barbed portion 409 to engage acorresponding locking feature on a mating connector on the dialysismachine, and a finger depression portion 410 to aid in disengaging thebarbed portions 409 from the dialysis machine. The barbed portion 409helps to lock the frustoconical member in sealing engagement with itsmating connector on the dialysis machine when making a press-in type ofconnection. The distal ends of the locking arms can be constructed toattach to the connector via a flange 411 located proximal to thefrustoconical portion 407 of the connector 400. The connector 400 has aproximal tubing attachment end 402 to sealingly engage a flexible tube.The tubing attachment end 402 may have one or more barb features 412 tohelp prevent disengagement of the end of a flexible tube from theconnector 400.

FIG. 43B shows a side view of connector 400, bringing into view anaccess feature or port 420 that can permit placement of an electrode indirect communication with the lumen of connector 400. In otherembodiments, the access feature may house an elastomeric stopper—with orwithout a septum—to permit sampling of fluid from within the lumen 414of connector 400 using a syringe with a sharp or blunt needle.Alternatively, the feature may serve as a port to allow connection ofanother fluid line to the lumen 414 of connector 400.

In yet another embodiment, the mid-portion 406 of connector 400 may havetwo access ports, as shown in the cross-sectional view of FIG. 43C. Afluid access port 420 a can serve as a sampling port, and an electrodeport 420 b can serve as an electrode cradle. An elastomeric stopper 422within sampling port 420 a can be shaped to extend to the lumen 414 ofconnector 400, simultaneously permitting sampling of fluid in the lumen414 with a needle, while maintaining an air-tight seal. Alternatively, aLuer-type connector having a septated cap or seal can be incorporatedinto the port, which is capable of connecting with a syringe or catheterhaving a mating Luer-type connector. An electrode port 420 b can serveas a seat or cradle for an electrode 424. In can be press-fit orcemented into position, and sealed with an adhesive, or with an O-ring416 as shown. A wire 426 can be soldered, welded or otherwise securedonto the outer surface of electrode 424, and can travel proximallytoward dialysis machine 200 with the arterial tubing 108 or venoustubing 126 to which connector 400 is attached.

In any of the above electrode embodiments, the electrodes may bereplaced by a suitably sized thermistor, or combination of a thermistorand electrical conductor, for the additional purpose of monitoring thetemperature of the fluid passing through connector 300, 400 or variantsthereof.

Wire Assembly

In one embodiment, the wires carrying electrical signals to or from apair of electrodes on connectors 106, 128 (one on the arterial side andone on the venous side of the blood flow circuit) can travel separateand apart from the blood tubing 108, 126 back toward dialysis machine200, where they ultimately terminate and connect to, a conductivitydetecting circuit, such as the conductivity circuit shown in FIG. 37.The conductivity circuit, in turn, provides an appropriately configuredsignal to a processor on the dialysis machine to determine whether achange in fluid conductivity consistent with an access disconnection hasoccurred. If so, the processor can trigger an alarm condition, or caninitiate a shut-down of blood pump 13, and trigger a mechanicalocclusion of blood tubing 108 and/or 126, for example.

Wires that extend together or separately between the dialysis machineand the patient are at risk of getting tangled, broken or becomingdisconnected. Therefore, preferably, each wire 326 or 426 can beattached, fused, or otherwise incorporated into its associated tubing108, 128. Incorporating a wire into its associated tubing provides aconvenient way of protecting the wires and connections, and simplifyingthe interface between the patient and the dialysis apparatus. Exemplarymethods of achieving this are shown in FIGS. 44A-44D. In a preferredembodiment, the tubing is comprised of a flexible material (e.g.,silicone) that can be formed in an extrusion process. As shown in FIG.44A, a loose wire mesh may be embedded in the flexible silicone tubingas it is formed and extruded, similar to fiber reinforcement of flexibletubing. As shown in FIG. 41A, a wire mesh 500 can be embedded within thewall of the flexible tubing 502 during extrusion, in a manner similar tothe construction of a fiber-reinforced tube. As shown in FIG. 44B, aninsulated wire 504 can be joined to the external surface of its adjacenttubing 506, either during a secondary extrusion process, or a process inwhich the two structures are joined by an adhesive, for example. Asshown in FIG. 44C, a second extrusion producing a secondary concentriclayer of tubing material 508 can be made to capture a wire running alongthe external surface of the tubing after the primary extrusion. As shownin FIG. 44D, the tubing 502 during formation can also be co-extrudedwith a wire 504 embedded in the wall of the tubing.

In some of the above methods, the resulting tube-wire combination mayhave a tendency to curl because of the difference in thermalcoefficients of expansion between the wire and the silicone material ofthe tubing. As the material cools after extrusion, the silicone maycapture the embedded wire tightly, causing the cooled tube-wire bundleto curl. In a preferred embodiment, the wire lumen of the extrusion dieis constructed to be large enough to accommodate a cross-sectional areasignificantly larger than the cross-sectional area of the wire to beembedded. Then as the silicone cools, the passageway surrounding thewire does not shrink to the point of tightly encasing the wire. Aco-extrusion process incorporating an insulated wire can generate atube-wire bundle as shown in FIG. 45. In this example, flexible tubing502 is a co-extrusion of a fluid-carrying lumen 601 and a wire-carryinglumen 602. Preferably, the wire 501 is multi-stranded for flexibilityand durability, and is coated or sheathed in a durable, flexiblesynthetic insulating material 503, such as, for example, PTFE. APTFE-based sheath 503 of the stranded wire 501 can sustain the hightemperatures associated with the silicone tubing extrusion process, sothat its integrity is maintained along the section 504 of the wire thatultimately exits the tubing for connection either to the dialysismachine 200 or the patient line connectors 106, 128. A coating orsheathing may also help prevent the wire from adhering to the side wallsof the wire-carrying lumen after extrusion and during cooling.

FIG. 46 shows a cross-sectional view of an exemplaryconnector-wire-tubing assembly. The proximal tubing connection end of aconnector 400 is shown with the end of a double-lumen tubing 502attached. The fluid-carrying lumen 601 is press-fit and/or cemented tothe proximal end of connector 400, allowing for fluid flow through thecentral lumen 414 of connector 400. Stranded wire 501 is soldered orotherwise attached to electrode 424, which is in conductive contact withany fluid present within the lumen 414 of connector 400. Thenon-connecting portion of the wire 501 that travels outside tubing 502is preferably sheathed in an insulating synthetic coating, such as, forexample, PTFE. Optionally, this portion of both the exposed and sheathedwire may also be sealed with a sealant, such as RTV. The sheathed wire503 enters the wire-carrying lumen 602 of tubing 502 near itstermination onto connector 400. The wire/tubing bundle then makes itsway toward the dialysis machine 200, where the wire emerges from thetubing to make a connection to a conductivity circuit such as the oneshown in FIG. 37.

FIG. 47 shows an exemplary extracorporeal circuit 210 that may be usedas a removable, replaceable unit in a hemodialysis apparatus 220 asshown in FIG. 48. In this embodiment, the extracorporeal circuitcomprises a blood pump cassette 13, dialyzer 14, venous return air trap122, arterial blood tubing 108, venous blood tubing 126, arterialcatheter connector 106, and venous catheter connector 128. The arterial106 and venous 128 connectors may be of a type similar to the connector300 shown in FIGS. 41A and 41B, or similar to the connector 400 shown inFIGS. 43A-43C, or variants thereof. The arterial 108 and venous 126blood tubes may be of a type shown in FIGS. 44A-44D, or FIG. 45. Wiresforming terminal connections to electrodes on connectors 106 and 128 mayexit arterial 106 and venous 126 tubes as segments 504A and 504B to makea connection with a connector that ultimately passes the connectionthrough on the dialysis apparatus to terminals associated with aconductivity circuit such as that shown in FIG. 37. In the embodimentshown, the connector 526 is mounted to a support structure 214 for theblood pump 13 and air trap 122.

FIG. 48 shows an exemplary hemodialysis apparatus 220 that is configuredto receive the extracorporeal circuit 210 shown in FIG. 47. In thisillustration, the dialyzer 14 is already mounted onto the apparatus 220.A base unit 227 receives the control ports of a mating blood pumpcassette 13. Sets of raceways or tracks 225 help to organize the pair ofarterial 106 and venous 126 blood tubes when not extended out andconnected with a patient. A connector 224 receives and passes throughthe connections made between wire segments 504A and 504B and connector526 to the terminal connections of a conductivity circuit such as thatshown in FIG. 1. A tubing occluder 226 is positioned to receive venousblood tube 126 after it exits air trap 122, and arterial blood tube 108before it reaches blood pump cassette 13. The occluder 226 may beactuated pneumatically or electromechanically, for example, whenever analarm condition occurs that requires cessation of extracorporeal bloodflow. A set of arms of occluder 226 can be configured to rotate againstthe walls of the flexible tubes, constricting or stopping fluid flowwithin them. Thus, a controller installed within apparatus 220 canreceive a signal from a conductivity circuit similar to FIG. 37, thesignal representing the electrical resistance of the column of fluid orblood between the electrodes mounted on connectors 106 and 128. Becausethe connectors are positioned much closer fluidically to the patient'sblood vessel or fistula 134 than to the blood pump 13, dialyzer 14 andair trap 122, the signal associated with the fluid path through theblood vessel or fistula 134 can discriminate between an intact and aninterrupted column of blood or fluid between the connectors 106/128 andthe patient's blood vessel or fistula 134. The controller can beprogrammed to respond to an electrical resistance detected by theconductivity circuit found to exceed a pre-determined value. Dependingon the circumstances, the controller may then trigger an alarm to alertthe patient to a possible disconnection of blood flow, and may alsooptionally command the occluder 226 to cease extracorporeal flow to andfrom the patient.

Operation of the Disconnect Detection Circuit

FIG. 49 shows test results utilizing the disconnect detection circuitdescribed above and shown in FIG. 37. In this case, a hemodialysis bloodcircuit and apparatus was employed that is similar to that disclosed inU.S. Patent Application Publication Nos. 2009/0114582 and 2010/0056975,(the contents of which are hereby incorporated by reference). Theextracorporeal circuit 210 shown in FIG. 47, comprises a blood pump 13,dialyzer 14, air trap 122, venous blood circuit tubing 126, and arterialblood circuit tubing 108. Extracorporeal circuit 210 mates to ahemodialysis apparatus 220 similar to the one shown in FIG. 48. Theblood flow circuit tested included a pair of membrane-based blood pumpsarranged on a blood pump cassette 13 shown in FIG. 47, a dialyzer 14, avenous return air trap 122, an arterial blood tubing set 108, a venousblood tubing set 126, arterial and venous connectors 106 and 128, andcatheter tubing sets 104, 130 connected to vascular access needles 102,132 as shown in FIG. 40. The needles 102, 132 were placed in a containerholding anticoagulated bovine blood. The blood tubing set 108 and 126was approximately six feet long, and the catheter tubing sets 104 and130 were approximately two feet long or less. The needles werealternately manually placed in or withdrawn from the container duringblood flow to simulate disconnection of a needle from a fistula or bloodvessel. Periods A, C and F in FIG. 49 represent the times during whichthe needles were submerged in the blood in the container. The electricalresistance measured by the disconnect detection circuit shown in FIG. 37during these periods averaged between 120,000 and 130,000 ohms. PeriodsB and E in FIG. 49 represent the times during which the venous returnneedle 132 (under positive pressure from the blood pumps) was withdrawnseveral centimeters above the surface of the blood within the container,forming a stream of blood mixed with air as the blood exited the venousreturn needle and entered the container of blood below. The electricalresistance measured during these periods averaged between 140,000 and150,000 ohms. Period D represents the time during which one of theneedles was completely removed from the container, creating a fully openelectrical circuit. The electrical resistance measured during thisperiod averaged between about 160,000 and 180,000 ohms. Thus acontroller can be readily programmed to distinguish the difference inthe monitored resistance of the electrical circuit between anuninterrupted and an interrupted flow of blood. These results showedthat an interruption of the continuity of the blood between the arterial102 and venous 132 needles can reliably produce a detectable change inthe measured electrical resistance between two electrodes when placedrelatively closer to the arterial and venous access sites than to theblood processing components 13, 14 and 122 of the extracorporeal bloodcircuit. Furthermore, even a partial interruption of the continuity ofblood flow (as in the streaming of blood through air) can be reliablydetected, albeit with a smaller change in the measured electricalresistance.

Occluder

As mentioned above, an occluder, such as the occluder 513 in FIG. 17,can be used to control flow through lines of a blood circuit assembly,e.g., at a point between a patient connection of the blood lines 203,204 and other portions of the assembly. Below, various aspects of theinvention relating to an occluder, which may be employed alone or in anysuitable combination with other features described herein, aredescribed, along with one or more specific embodiments.

In accordance with one aspect of the disclosed invention, an occlusionassembly for compressing at least one flexible tube, for example a pairof flexible tubes is described. The occlusion assembly includes a tubeoccluder comprising a mechanism configured to occlude fluid flow withinone or more flexible tubes, and in certain embodiments one or more pairsof flexible tubes. In certain embodiments, the tube occluder of theocclusion assembly comprises at least one occluding member, and in aspecific embodiment comprises an occluding member for each section oftubing placed within the assembly. In certain such embodiments, eachoccluding member is pressed or otherwise forced or urged into anoccluding position by an element that slides along a side of theoccluding member, causing the occluding member to pivot at its proximalend and to translate toward the tubing at its distal end. In anembodiment, the element is positioned between two occluding members andacts to spread the distal ends of the occluding members away from eachother as they press against their respective tubes. In a preferredoption, a main spring urges the spreading element toward the distal endsof the occluding elements into an occluding position. The spreadingelement may be moved against the biasing force of the main spring into anon-occluding position near the proximal ends of the occluding elementseither manually through a button and linkage assembly coupled to thespreading element, or by control of a controller activating an actuatorthat is also coupled to the spreading element. A hinged door may beconfigured to cover the occluding elements and their respective sectionsof tubing. Activation of the actuator may be prevented if the door isnot properly closed over the occluding elements. Optionally, a retentionelement to hold the spreading element in a non-occluding position may beenabled when the door is in an open position. Enabling the retentionelement allows the spreader to be held in a non-occluding positionwithout continued application of force by a user on the button or bycontinued activation of the actuator. The retention element may bedisabled when the door is closed, so that the spreading element may befree to be moved into and out of an occluding position, either manuallyor via the actuator.

FIGS. 50 and 51 show exploded, perspective views of an occlusionassembly 700 in accordance with an embodiment of the present disclosure.FIG. 50 shows an exploded, perspective view of the occlusion assembly700 from a front angle and FIG. 51 shows an exploded, perspective viewof the occlusion assembly 700 from a back angle.

The occlusion assembly 700 receives a pair of tubes 705 and isconfigured to occlude the tubes 705 using a pinching action atapproximately the same level along the length of assembly 700. Thepinching action reduces the size of an inner fluid pathway of each tube705 to restrict the flow of fluid therethrough. The occlusion assembly700 may be used with an infusion pump, in a dialysis machine, inhemodialysis, in peritoneal dialysis, in hemofiltration, inhemodiafiltration, in intestinal dialysis, and the like.

The occlusion assembly 700 includes a frame 701. In some embodiments,the frame 701 includes tabs or snaps 709 for securing the frame tocorresponding slots on a front panel of a blood filtration device, suchas a hemodialysis apparatus.

The frame 701 includes anvils or blocks 702 and 703 against which a tube705 is compressed by the occluding ends 713 of a pair of occluding arms710 and 711, and a tube guide 704 to position each tube 705 againstblocks 702 and 703. The tube guide 704 and blocks 702 and 703 areconfigured to each position a tube 705 in a predetermined positionadjacent to each of the blocks 702 and 703. The occlusion assembly 700also includes a door 706 which is pivotally mounted to the frame 701.The door 706 can shut against the frame 701 to secure the tubes 705between each of the blocks 702 and 703 and the tube guide 704. The door706 includes a latch 707 co-molded with the door 706 via a resilient,flexible base portion (e.g., via a living hinge) 708 to secure the door706 to the frame 701 in a closed position. However, the latch 707 couldbe arranged in other suitable ways, such as including a latch elementthat is adhered, welded, bolted or otherwise attached to the door 706.As shown in FIGS. 50, 52 and 53, the latch 707 may be pressed laterallyto release a catch 740 from engagement with a corresponding slot 741 onframe 701 to open the door 706.

The occlusion assembly 700 includes two arms 710 and 711. The first arm710 includes a pivoting end 712 and an occluding end 713; likewise, thesecond arm 711 includes a pivoting end 714 and an occluding end 715. Thetwo arms 710 and 711 operate together to occlude the tubes 705 when abutton 716 is released and door 706 is closed, or when an actuator 717is deactivated.

FIG. 52 shows a front, perspective view of the occlusion assembly 700with the door 706 open and the button 716 pressed to illustrate releaseof occluding arms 710 and 711 to permit loading and unloading of thetubes 705 in accordance with an embodiment of the present disclosure.FIG. 54 shows the front of the occlusion assembly 700 of FIG. 50 withoutthe door 706 and frame 701 to illustrate the arms 710 and 711 fullyoccluding the tubes 705 a, b in accordance with an embodiment of thepresent disclosure. As shown in FIG. 54, a wedge element or spreader 722contacts the facing sides of occluding arms 710 and 711, which underspring force can apply pressure to occluding arms 710 and 711 to pressthe occluding ends 713 and 715 of occluding arms 710 and 711 against aportion of tubes 705 a, b. A user may release the occluding arms 710 and711 by pressing button 716, which causes spreader 722 to withdraw awayfrom occluding arms 710 and 711, releasing the pressure of spreader 722being applied to the distal ends of occluding arms 710 and 711. In someaspects, the manual actuator (e.g. button 716) acts as an overridemechanism to an automated actuator (such as, for example, apneumatically operated piston/cylinder apparatus) connected to a tubingoccluder element (e.g., the spreader 722). The manual actuator isoperatively coupled to the tubing occluder to cause essentially linearmotion of at least a portion of the tubing occluder, moving theoccluding member from an occluding position to a non-occluding positionupon manual operation of the override mechanism by a user.

Similarly, activation of an actuator may release occluding arms 710 and711 by causing spreader 722 to withdraw away from the occluding ends713, 715 of occluding arms 710 and 711. In one embodiment, as shown inFIG. 50, spreader 722 may be formed of, co-molded with, attached to orotherwise connected to a carriage assembly 723, which in turn isconnected to an actuating arm of the actuator (see, e.g., FIGS. 56 and57). The actuator may comprise, for example, a motor and gear assembly(e.g., rack and pinion assembly or worm-type gear assembly), a solenoid,a hydraulic cylinder or a pneumatic cylinder, among others. In apreferred embodiment, the actuator comprises a pneumatic cylinder 717that causes an actuating arm comprising a piston arm 742 to extendlinearly against a spring force (which in an embodiment may be a coilspring 745 within cylinder 717 as shown in FIG. 60). As shown in FIG.60, in a perspective side view of a pneumatically operated linearactuator 717, piston arm 742 is connected to carriage 723. Whenactivated by pneumatic pressure, actuator 717 extends piston arm 742 andmoves carriage 723 and attached spreader 722 in a direction thatwithdraws spreader 722 from engagement with the distal ends 713, 715 ofthe occluding arms 710 and 711. (For clarity, occluding arm 711, frame701, door 706, block 703 and tube guide 704, among other elements, havebeen removed from FIGS. 58-60). Preferably, a main spring that is eitherexternal or internal to cylinder/actuator 717 may apply a biasing forceto piston arm 742 or carriage 723 to cause spreader 722 to moveoccluding arms 710 and 711 to an occluding position. In the event of aloss of power or pneumatic pressure, the occluding arms 710 and 711 willdefault to an occluding mode, preventing the flow of fluid through tubes705. As illustrated in a cross-sectional view of occlusion assembly 700in FIG. 60, in an embodiment, a coil spring 745 may be placed within thecylinder 743 to provide a biasing force against which piston 744 maymove piston arm 742 under pneumatic pressure. Pneumatic pressure may besupplied to linear actuator 717 from a pressure source (e.g., a tankpressurized by a pump) regulated by an intervening electromechanicalvalve under control of an electronic controller.

As shown in FIGS. 54 and 59, when the linear actuator 717 is fullyretracted, the carriage 723 carries spreader 722 along the facing sidesof the occluder arms 710 and 711 to rotate them into an occludingposition. The first arm 710 pivots about its pivoting end 712 to causethe occluding end 713 to press against first tube 705 a that isrestrained by block 702 (see FIG. 54). The second arm 711 pivots aboutits pivoting end 714 such that the occluding end 715 can press againstsecond tube 705 b which is restrained by block 703.

FIGS. 55 and 58 show occlusion assembly 700 in a non-occluding state(frame 701, door 706. Blocks 702, 703, and other elements removed forclarity). When the button 716 is pressed or the linear actuator 717 isactivated, the carriage 723 and attached spreader 722 move distally awayfrom the actuator 717, allowing occluder arms 710 and 711 to rotateabout pivot points 712 and 714 into a non-occluding position. Theelastic resilience of the tubes 705 a, b may cause the arms 710 and 711to pivot towards each other. In some embodiments of the presentdisclosure, small magnets (not explicitly shown) embedded in the arms710 and 711 pull the arms 710 and 711 towards each other to facilitatethe retraction of the occluding ends 713 and 715 away from the tubes705. In other embodiments, small springs (not shown) may bias occludingarms 710 and 711 to pivot toward each other, the spring constants beingweak enough to be overcome by the main spring (e.g., spring 745) biasingcarriage 723 or spreader 722 into retracted (occluding) positions.

FIG. 53 shows a perspective side view of the occlusion assembly 700 ofFIG. 50 (frame 701 removed for clarity) showing the door 706 engaging aswitch 720 when the door 706 is closed in accordance with an embodimentof the present disclosure. As shown in FIG. 53, the hinge portion 708 oflatch 707 is coupled to an engagement member or catch 740 that can snapinto a cooperating slot 741 of the frame 701 (see, e.g., FIGS. 50 and53). As the door 706 is closed, a portion of the catch 740 of latch 707of the door 706 engages a spring-loaded switch 720, which in anembodiment includes a spring arm 737 of the switch 720.

Engagement of switch 720 by closure of door 706 signals an electroniccontroller (not shown) that the door 706 is properly closed, and thatlinear actuator 717 may be activated to release occluders 710 and 711 toallow fluid to flow through tubes 705. The door 706 closure signal mayalso cause the controller to perform other functions, such as, forexample, instructing a pump coupled to the tubes 705 to begin pumpingfluid within tubes 705.

FIG. 56 shows the back of the occlusion assembly 700 of FIG. 50 with thelinear actuator 717 in a fully retracted position (i.e., in theoccluding position) in accordance with an embodiment of the presentdisclosure. FIG. 56 shows the back side of the occlusion assembly 700 inthe same configuration as shown for the front view of occlusion assembly700 in FIG. 54. FIG. 56 shows several working parts of the occlusionassembly 700 of FIG. 50 to illustrate the operation of the actuator 717and carriage 723 in accordance with an embodiment of the presentdisclosure. The carriage 723 moves with the extension or retraction ofthe piston arm 742 or with the actuation of the button 716. The carriage723 includes guides 724 co-molded with or otherwise attached to thecarriage 723. The guides 724 guide the carriage 723 as it moves viaactuation of the piston arm 742 or with the actuation of the button 716.The guides 724 interface with tracks 725 of the frame 701 (see, e.g.,FIG. 51).

In an optional embodiment, when door 706 is open, actuation of button716 by a user or activation of actuator 717 by a controller causescarriage 723 and spreader 722 to move into a non-occluding position, anda retaining element or assembly allows the non-occluding position to beheld without further force being applied either by the user or by theactuator 717. In an exemplary embodiment shown in FIG. 56, the carriage723 may incorporate a latching pin 726 to cooperate with a slot or holein a retention member 718. The retention member 718 includes a surface727 positioned to be contacted by pins 738 located on the inside of door706 when it is closed (see, e.g., FIGS. 51 and 52). Through holes 739allow pins 738 to contact a portion of retention member 718 to displaceit in a rearward direction. In the illustrated embodiment, pins 738contact front plate 727 of retention member 718. Retention member 718also includes a surface having a slot or hole 729 positioned to receivethe head of a latching pin 726, which in the illustrated embodimentcomprises a horizontal plate 728 defining a receiving portion 729.Retention member 718 is arranged to slide within grooves or guides ofthe frame 701 (not shown) in response to contact by the pins 738 whenthe door 706 is closed or opened (see, e.g. FIG. 51). A spring 730mounted on the frame 701 may be biased to urge the retention member 718forward to a stop feature (not shown) on the frame 701 so that openingthe door 706 allows the retention member 718 to slide forward,re-aligning the receiving portion 729 in relation to the latching pin726. When the door 706 is closed (see FIG. 50 or 51), the pins 738 onthe door 706 press against the front plate 727 which compresses thespring 730 such that the receiving portion 729 of the horizontal plate728 is positioned directly over the latching pin 726. Upon alignment ofthe receiving portion 729 with the latching pin 726, the area of thereceiving portion 729 is large enough to allow the latching pin 726 tobe released by the retention member 718, thereby allowing the carriage723 to be subject to the spring force of the main spring 745 in theactuator 717. If pneumatic pressure is not then being applied to theactuator 717, the carriage 723 is then free to move into an occludingposition. The retention member 718 in the disabled state (i.e.,inoperative state) allows the latching pin 726 to move freely throughthe receiving portion 729 as the carriage 723 moves between the fullyextended position and the fully retracted position.

FIG. 57 is a rear view of the occlusion assembly 700 with the actuator717 activated, and the piston arm 742 in an extended position to placethe occluding arms 710, 711 in a non-occluding state. In this view, thehead of the latching pin 726 is noted to be above the plane of thehorizontal plate 728 of the retention member 718, and the recessedregion 731 of the latching pin 726 is noted to be aligned with thereceiving portion 729 of the retention member 718. In this illustration,door 706 is in a closed position, implying that the receiving portion729 is in a sufficiently rearward position to prevent the latching pin726 from being latched into the retention member 718.

When the door 706 is sufficiently opened, the pins 738 of the door 706do not press against the front plate 727 and the spring 730 applies aforce on the front plate 727 such that the receiving portion 729 of theretention member 718 is positioned to allow the latching pin 726 toengage an edge of the receiving portion 729 and latch to the retentionmember 718. The latching pin 726 moves into the receiving portion 729pulling the front plate 727 rearward against the force of the spring 730when the receiving portion 729 is positioned to latch to the latchingpin 726. When the head of latching pin 726 moves sufficiently throughthe receiving portion 729, a recessed region 731 below the head oflatching pin 726 becomes co-aligned with the horizontal plate 728 whichmoves as the edge of the receiving portion 729 moves into the recessedregion 731 under the force of the spring 730 as applied to the frontplate 727. When the pins 738 of the door 706 sufficiently engage thefront plate 727, the receiving portion 729 is positioned to release thelatching pin 726 from the latch 718. Thus, when the door 706 is open,the carriage 723 and spreader 722 can be held in a non-occludingposition without the continuous application of force by the actuator 717or by a user pressing against the button 716. This permits a user toload and unload tubing from occlusion assembly 700 withoutsimultaneously having to apply force on the button 716. However, uponthe closing of the door 706, the retention member 718 is no longeroperative, and in the absence of continued application of force byeither the actuator 717 or through the button 716, the carriage 723 andspreader 722 will move into a position to cause the occluding arms 710and 711 to rotate to an occluding position.

FIGS. 58 and 59 show a side perspective view of several working parts ofthe occlusion assembly 700 of FIG. 50, with frame 701, blocks 702, 703,tube guide 704, door 706, occluding arm 711 and other parts removed forclarity. In FIG. 58, the piston arm 742 is fully extended in accordancewith an embodiment of the present disclosure. FIG. 58 shows the latchingpin 726 latched onto the retention member 718. That is, assuming thatdoor 706 is in an open position, the horizontal plate 728 is positionedby the force of spring 730 to engage the recessed region 731 of thelatching pin 726.

FIG. 59 shows a side, perspective view of the occlusion assembly 700 ofFIG. 50 with the piston arm 742 in a fully retracted position, withcertain elements removed as in FIG. 58 for clarity. In this example, thelatching pin 726 is shown to be completely disengaged from the retentionmember 718; and in the absence of an activating force on the actuator717 or a pressing force on the button 716, the piston arm 742, carriage723 and spreader 722 are free to retract under the force of a mainspring 745 (see FIG. 60) biased against the extension of piston arm 742.The spreader 722 then moves toward the occluding ends 713, 715 of theoccluding arms 710, 711. In an embodiment, as shown in FIGS. 58 and 59,the button 716 pivots about a pivot 732 to raise a lever arm 733 whenthe button 716 is pressed. The lever arm 733 is pivotally connected to aconnecting member 734 via a proximal pivot 735. The connecting member734 in turn is pivotally connected to the carriage 723 via a distalpivot 736. When the button 716 is pressed or the piston arm 742 movesthe carriage 723 toward the retention member 718, the connecting member734 moves with the carriage 723, rotating the button 716 about the pivot732 as shown in FIG. 58.

FIG. 61 shows the occlusion assembly 700 of FIG. 50 used in afront-panel assembly 911 of a dialysis system in accordance with anembodiment of the present disclosure. The occlusion assembly 700occludes flexible tubes 901, 902 through which blood flows to and from apatient. The right side tube 902 carries blood from a patient into ablood pump assembly 1000 (an arterial blood line) and the left side tube901 carries blood from a dialyzer 14 back to the patient after passingthrough an air trap 19 (a venous blood line). The occlusion assembly 700can occlude the flow of blood through both of these patient tubes 901,902 simultaneously.

As discussed in detail above, the tubes 901, 902 are connected to ablood pump cassette or assembly 1000, which is a modular unit that maybe mounted onto and dismounted from the front-panel 911. Both of thepatient tubes 901, 902 may be provided as an assembly with the bloodpump cassette 1000 and air trap 19, and may be loaded into the occlusionassembly 700 when the blood-pump cassette 1000 is mounted onto thefront-panel 911. In this embodiment, the occlusion assembly 700 forms apermanent part of the front panel 911.

When the occlusion assembly 700 is in the non-occluding state, pumpslocated on blood pump cassette 1000 may be activated to pump blood froma patient through the right tube 902, up through the blood pumps andthrough a dialyzer 14. Blood processed by the dialyzer 14 then returnsto the patient via tube 901 after first passing through an air trap 19and an air-in-line detector 823.

The following are each incorporated herein by reference in theirentireties: U.S. Provisional Patent Application Ser. No. 60/903,582,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods”; U.S.Provisional Patent Application Ser. No. 60/904,024, filed Feb. 27, 2007,entitled “Hemodialysis System and Methods”; U.S. patent application Ser.No. 11/787,213, filed Apr. 13, 2007, entitled “Heat Exchange Systems,Devices and Methods”; U.S. patent application Ser. No. 11/787,212, filedApr. 13, 2007, entitled “Fluid Pumping Systems, Devices and Methods”;U.S. patent application Ser. No. 11/787,112, filed Apr. 13, 2007,entitled “Thermal and Conductivity Sensing Systems, Devices andMethods”; U.S. patent application Ser. No. 11/871,680, filed Oct. 12,2007, entitled “Pumping Cassette”; U.S. patent application Ser. No.11/871,712, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,787, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,793, filedOct. 12, 2007, entitled “Pumping Cassette”; and U.S. patent applicationSer. No. 11/871,803, filed Oct. 12, 2007, entitled “Cassette SystemIntegrated Apparatus.” In addition, the following are incorporated byreference in their entireties: U.S. Pat. No. 4,808,161, issued Feb. 28,1989, entitled “Pressure-Measurement Flow Control System”; U.S. Pat. No.4,826,482, issued May 2, 1989, entitled “Enhanced Pressure MeasurementFlow Control System”; U.S. Pat. No. 4,976,162, issued Dec. 11, 1990,entitled “Enhanced Pressure Measurement Flow Control System”; U.S. Pat.No. 5,088,515, issued Feb. 18, 1992, entitled “Valve System withRemovable Fluid Interface”; and U.S. Pat. No. 5,350,357, issued Sep. 27,1994, entitled “Peritoneal Dialysis Systems Employing a LiquidDistribution and Pumping Cassette that Emulates Gravity Flow.” Alsoincorporated herein by reference are a U.S. patent application entitled“Sensor Apparatus Systems, Devices and Methods,” filed on even dateherewith (Docket No. F63, now Ser. No. 12/038,474), and a U.S. patentapplication entitled “Cassette System Integrated Apparatus,” filed oneven date herewith (Ser. No. 12/038,648).

While several embodiments of the present invention have been describedand illustrated herein, those of ordinary skill in the art will readilyenvision a variety of other means and/or structures for performing thefunctions and/or obtaining the results and/or one or more of theadvantages described herein, and each of such variations and/ormodifications is deemed to be within the scope of the present invention.More generally, those skilled in the art will readily appreciate thatall parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the teachings of thepresent invention is/are used. Those skilled in the art will recognize,or be able to ascertain using no more than routine experimentation, manyequivalents to the specific embodiments of the invention describedherein. It is, therefore, to be understood that the foregoingembodiments are presented by way of example only and that, within thescope of the appended claims and equivalents thereto, the invention maybe practiced otherwise than as specifically described and claimed.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

What is claimed is: 1.-52. (canceled)
 53. A blood circuit assemblyengagement device for a dialysis unit, comprising: an actuator movablymounted to a panel of the dialysis unit adjacent a plurality of controlports that are configured to connect with mating control ports on a backside of a blood circuit assembly, the actuator movable between aretention position and an ejection position; a retainer element coupledto the actuator and arranged, with the actuator in the retentionposition, to contact a portion of a front side of the blood circuitassembly, and retain the blood circuit assembly on the panel of thedialysis unit, and arranged, with the actuator in the ejection position,to release the blood circuit assembly for removal from the panel of thedialysis unit; and an ejector element coupled to the actuator or to thepanel and arranged, with the actuator moved from the retention positionto the ejection position, to contact a portion of the back side of theblood circuit assembly to urge the blood circuit assembly away from thepanel.
 54. The blood circuit assembly engagement device of claim 53,wherein the actuator is pivotally mounted to the panel.
 55. The bloodcircuit assembly engagement device of claim 53, wherein the retainerelement is fixed to or formed with the actuator.
 56. The blood circuitassembly engagement device of claim 53, wherein the ejector element ispivotable between an inactive or retracted position and an ejectionposition.
 57. The blood circuit assembly engagement device of claim 53,wherein the actuator is arranged to be moved from the retention positionto the ejection position by a user's thumb.
 58. The blood circuitassembly engagement device of claim 53, comprising first and secondblood circuit assembly engagement devices, the first engagement devicepositioned on a first side of the blood circuit assembly mounted to thepanel, and the second engagement device positioned on a second side ofthe blood circuit assembly mounted to the panel, the first and secondsides being opposed to each other such that the actuators of theengagement devices are movable by respective first and second thumbs ofa user.
 59. The blood circuit assembly engagement device of claim 58,wherein the actuators are movable away from each other from respectiveretention positions to ejection positions.
 60. The blood circuitassembly engagement device of claim 53, wherein the ejector element isarranged to contact a portion of a pump chamber of the blood circuitassembly in the ejection position.
 61. The blood circuit assemblyengagement device of claim 53, wherein the retention element comprisestwo opposing arms, and is arranged, with the actuator in the retentionposition and a blood circuit assembly mounted to the panel, to contactan outer surface of the blood circuit assembly at two locations to lockthe blood circuit assembly in place.
 62. The blood circuit assemblyengagement device of claim 53, wherein the actuator is spring biased tomove toward the retention position. 63.-82. (canceled)
 83. The bloodcircuit assembly engagement device of claim 60, wherein a portion of theejector element adjacent the contacting portion of the pump chamber ispositioned in a recess when the blood circuit assembly is mounted on thepanel and the ejector element is in an inactive or retracted position.84. The blood circuit assembly engagement device of claim 56, whereinthe ejector element is pivotable about an axis, with a proximal portionon a first side of the axis configured to contact an ejector contact armof the actuator, and a distal portion on a second opposing side of theaxis configured to make contact with the blood circuit assembly.
 85. Theblood circuit assembly engagement device of claim 84, wherein theejector contact arm of the actuator is configured to depress theproximal portion of the ejector element and raise the distal portion ofthe ejector element into an ejection position when the actuator isdepressed and placed in an ejection position.
 86. A blood circuitassembly engagement device for a dialysis unit, comprising: a pair ofactuators movably mounted to a panel of the dialysis unit adjacent toand on opposing sides of a plurality of control ports that areconfigured to connect with mating control ports on a back side of ablood circuit assembly, the actuators movable between a retentionposition and an ejection position; a pair of retainer elements, eachcoupled to a respective actuator and arranged, with the actuators in theretention position, to contact portions of a front side of the bloodcircuit assembly, and retain the blood circuit assembly on the panel ofthe dialysis unit, and arranged, with the actuator in the ejectionposition, to release the blood circuit assembly for removal from thepanel of the dialysis unit; and a pair of ejector elements, each coupledto a respective actuator or to the panel and arranged, with theactuators moved from the retention position to the ejection position, tocontact portions of the back side of the blood circuit assembly to urgethe blood circuit assembly away from the panel.
 87. The blood circuitassembly engagement device of claim 86, wherein the actuators arepivotally mounted to the panel.
 88. The blood circuit assemblyengagement device of claim 86, wherein the retainer elements are fixedto or formed with the actuator.
 89. The blood circuit assemblyengagement device of claim 86, wherein each ejector element is pivotablebetween an inactive or retracted position and an ejection position. 90.The blood circuit assembly engagement device of claim 86, wherein eachactuator is arranged to be moved from the retention position to theejection position by a user's thumb.
 91. The blood circuit assemblyengagement device of claim 86, wherein the actuators are movable awayfrom each other from respective retention positions to ejectionpositions.
 92. The blood circuit assembly engagement device of claim 86,wherein each ejector element is arranged to contact a respective portionof a pair of pump chambers of the blood circuit assembly in the ejectionposition.
 93. The blood circuit assembly engagement device of claim 86,wherein each retention element comprises two opposing arms, and isarranged, with the respective actuator in the retention position and ablood circuit assembly mounted to the panel, to contact an outer surfaceof the blood circuit assembly at two locations to secure the bloodcircuit assembly in place.
 94. The blood circuit assembly engagementdevice of claim 86, wherein each actuator is spring biased to movetoward the retention position.
 95. The blood circuit assembly engagementdevice of claim 92, wherein a portion of each ejector element adjacentthe contacting portion of the respective pump chamber is positioned in arecess when the blood circuit assembly is mounted on the panel and theejector element is in an inactive or retracted position.
 96. The bloodcircuit assembly engagement device of claim 89, wherein each ejectorelement is pivotable about an axis, with a proximal portion on a firstside of the axis configured to contact an ejector contact arm of therespective actuator, and a distal portion on a second opposing side ofthe axis configured to make contact with the blood circuit assembly. 97.The blood circuit assembly engagement device of claim 96, wherein theejector contact arm of each actuator is configured to depress theproximal portion of the respective ejector element and raise the distalportion of the respective ejector element into an ejection position whenthe actuator is depressed and placed in an ejection position.
 98. Ablood circuit assembly engagement device for a dialysis unit,comprising: an actuator movably mounted to a control port assembly ofthe dialysis unit, the control port assembly comprising a plurality ofpneumatic control ports configured to connect with mating valve and pumpcontrol ports on a back side of a blood circuit assembly, the actuatormovable between a retention position and an ejection position; aretainer element coupled to the actuator and arranged, with the actuatorin the retention position, to contact a portion of a front side of theblood circuit assembly, and secure the blood circuit assembly to thecontrol port assembly, and arranged, with the actuator in the ejectionposition, to release the blood circuit assembly for removal from thecontrol port assembly; and an ejector element coupled to the actuator orto the control port assembly and arranged, with the actuator moved fromthe retention position to the ejection position, to contact a portion ofthe back side of the blood circuit assembly to urge the blood circuitassembly away from the control port assembly.
 99. The blood circuitassembly engagement device of claim 98, wherein the actuator ispivotally mounted to the control port assembly.
 100. The blood circuitassembly engagement device of claim 98, wherein the retainer element isfixed to or formed with the actuator.
 101. The blood circuit assemblyengagement device of claim 98, wherein the ejector element is pivotablebetween an inactive or retracted position and an ejection position. 102.The blood circuit assembly engagement device of claim 98, wherein theactuator is arranged to be moved from the retention position to theejection position by a user's thumb.
 103. The blood circuit assemblyengagement device of claim 98, comprising first and second blood circuitassembly engagement devices, the first engagement device positioned on afirst side of the blood circuit assembly mounted to the control portassembly, and the second engagement device positioned on a second sideof the blood circuit assembly mounted to the control port assembly, thefirst and second sides being opposed to each other such that theactuators of the engagement devices are movable by respective first andsecond thumbs of a user.
 104. The blood circuit assembly engagementdevice of claim 103, wherein the actuators are movable away from eachother from respective retention positions to ejection positions. 105.The blood circuit assembly engagement device of claim 98, wherein theejector element is arranged to contact a portion of a pump chamber ofthe blood circuit assembly in the ejection position.
 106. The bloodcircuit assembly engagement device of claim 98, wherein the retentionelement comprises two opposing arms, and is arranged, with the actuatorin the retention position and a blood circuit assembly mounted to thecontrol port assembly, to contact an outer surface of the blood circuitassembly at two locations to lock the blood circuit assembly in place.107. The blood circuit assembly engagement device of claim 98, whereinthe actuator is spring biased to move toward the retention position.108. The blood circuit assembly engagement device of claim 105, whereina portion of the ejector element adjacent the contacting portion of thepump chamber is positioned in a recess when the blood circuit assemblyis mounted on the control port assembly and the ejector element is in aninactive or retracted position.
 109. The blood circuit assemblyengagement device of claim 101, wherein the ejector element is pivotableabout an axis, with a proximal portion on a first side of the axisconfigured to contact an ejector contact arm of the actuator, and adistal portion on a second opposing side of the axis configured to makecontact with the blood circuit assembly.
 110. The blood circuit assemblyengagement device of claim 109, wherein the ejector contact arm of theactuator is configured to depress the proximal portion of the ejectorelement and raise the distal portion of the ejector element into anejection position when the actuator is depressed and placed in anejection position.